NATO ASI Series Advanced Science Institutes Series

A series presenting the results of activities sponsored by the NATO Science Committee, which aims at the dissemination of advanced scientific and technological knowledge. with a view to strengthening links between scientific communities.

The series is published by an international board of publishers in conjunction with the NATO Scientific Affairs Division

A Life Sciences B Physics

C Mathematical and Physical Sciences

D Behavioral and Social Sciences E Engineering and

Materials Sciences

F Computer and Systems Sciences G Ecological Sciences

flecenf Volumes in this Series

Plenum Publishing Corporation New York and London

D Reidel Publishing Company Dordrecht. Boston, and Lancaster

Martinus Nijhoff Publishers The Hague. Boston, and Lancaster

Springer-Veriag Berlin, Heidelberg, New York, and Tokyo

Volume 89—Sensory Percept ion and Transduct ion in Aneural Organ isms edi ted by Giu l iano Co lombet t i , Francesco Lenci , and Pil l -Soon Song

Volume 90— Liver, Nut r i t ion , and Bile Ac ids edi ted by G. Gal l i and E. Bosis io

Volume 91—Recent Advances in Bio log ica l Membrane Stud ies: S t ruc ture and Biogenesis, Ox ida t ion and Energet ics edi ted by Lester Packer

Volume 92— Evolut ionary Relat ionships among Rodents: A Mul t id isc ip l inary Ana lys is edi ted by W. Patr ick Luckett and Jean-Louis Hartenberger

Volume 93— Biology of Invertebrate and Lower Vertebrate Co l lagens edi ted by A. Bairat i and R. Garrone

Volume 94—Cell T rans fo rmat ion edi ted by J. Cel is and A. Graessmann

Volume 95—Drugs Af fec t ing Leukotr ienes and Other E icosanoid Pathways edi ted by B. Samue lsson , F. Bert i , G. C. Folco, and G. Velo

Volume 96— Epidemio logy and Quant i ta t ion of Envi ronmenta l Risk in Humans f rom Radiat ion and Other Agents edi ted by A. Caste l lan i

Series A: Life Sciences

Epidemiology and Quantitati of Environmental Risk in Humans from Radiation and Other Agents Edited by

A. Castellani ENEA, Energy Research Center, Casacc ia Rome, Italy

Plenum Press New York and London Published in Cooperation with NATO Scientific Affairs Division

Proceedings of a NATO Advanced Study Inst i tu te on Epidemiology and Quant i ta t ion of Envi ronmental Risk in Humans f rom Radiat ion and Other Agents , held September 2 - 1 1 , 1984, in San Min ia to, Italy

NATO Advanced Study Inst i tu te on Epidemiology and Quant i ta t ion of Environ-Risk in Humans f rom Radiat ion and Other Agents (1984: San Min ia to , Italy) Ep idemio logy and quant i ta t ion of envi ronmenta l r isk in humans f rom rad ia t ion

and other agents. (NATO ASI series. Series A, Li fe sc iences; v. 96) "Proceed ings of a NATO Advanced Study Ins i tute on Epidemio logy and Quan­

t i ta t ion of Environmental Risk in Humans f rom Radiat ion and other Agents , held September 2 - 11 , 1984, in San Min ia to, I ta ly"

Bib l iography: p. Inc ludes index. 1. Rad ia t ion—Tox ico logy—Congresses . 2. Tox ico logy—Congresses . 3. Heal th

risk assessment—Congresses . I. Caste l lan i , Amle to . II. Ti t le. III. Series. RA1231.R2N363 1984 616.9'89707 85-19117 ISBN 0-306-42093-7

©1985 Plenum Press, New York A Div is ion of Plenum Publ ish ing Corporat ion 233 Spr ing Street, New York, N.Y. 10013 All r ights reserved No part of this book may be reproduced, stored in a retrieval system, or t ransmit ted, in any fo rm or by any means, e lect ronic , mechan ica l , pho tocopy ing , m ic ro f i lm ing , recording, or otherwise, w i thout wr i t ten permiss ion f rom the Publ isher Printed in the Uni ted States of Amer ica

Library of Congress Cata log ing in Pub l ica t ion Data

CONTENTS

R a d i a t i o n G a r c i n o g e n e s i s 1 E.E. P o c h i n

S t r a t e g y of Assessment of H e a l t h R i s k s i n E n v i r o n m e n t a l and O c c u p a t i o n a l H e a l t h 17

R.L. Z i e l h u i s

C h o i c e o f Comparison Groups i n E n v i r o n m e n t a l S t u d i e s and D e a l i n g w i t h Background M o r b i d i t y i n V a r i o u s S u b p o p u l a t i o n s 33

0. A x e l s o n

The P r o b a b i l i t y o f C a u s a t i o n : An Approach t o the P r o b l e m of T o x i c T o r t s , E s p e c i a l l y w i t h R e s p e c t t o Ex p o s u r e s t o I o n i z i n g R a d i a t i o n 47

S. J a b l o n

The C a r c i n o g e n i c E f f e c t s o f D i a g n o s t i c and T h e r a p e u t i c I r r a d i a t i o n 63

P.G. Smith

Dose-Response i n R a d i a t i o n C a r c i n o g e n e s i s : A n i m a l S t u d i e s ' 9 3

D.G. H o e l

Dose-Response i n R a d i a t i o n C a r c i n o g e n e s i s : Human S t u d i e s 105

D.G. H o e l

Fundamentals o f D o s i m e t r y and M i c r o d o s i m e t r y and the R e l a t i v e B i o l o g i c a l E f f e c t i v e n e s s o f I o n i z i n g R a d i a t i o n s 123

A.M. K e l l e r e r

C r i t i c a l Review o f C a s e - C o n t r o l and C o h o r t Study M e t h o d o l o g i e s 141

P.G Smith

vii

I n V i t r o M a l i g n a n t T r a n s f o r m a t i o n - a M u l t i - S t e p p e d P r o c e s s

J . J . McCormick and V.M. Mäher 157

P r o blems i n Dose Response and R i s k A ssessment: The Example o f A s b e s t o s 175

J . P e t o

R o l e o f DNA Damage and R e p a i r i n the M u t a g e n e s i s o f Human C e l l s by C a r c i n o g e n s 187

V.M. Mäher and J . J . McCormick

V a r i a t i o n s i n DNA R e p a i r Among P e o p l e 205 R.B. S e t l o w

C a n c e r - P r o n e F a m i l i e s : A Resource f o r E t i o l o g i c S t u d i e s 213

M.H. Greene

The R o l e o f Human RAS Proto-Oncogenes i n Cancer 225 S.R. T r o n i c k , A. Eva, S. S r i v a s t a v a , M. K r a u s ,

Y. Yuasa, and S. Aar o n s o n

H e r e d i t a r y and F a m i l i a l D i s o r d e r s L i n k i n g Cancer P r o n e n e s s w i t h Abnormal C a r c i n o g e n Response and F a u l t y DNA M e t a b o l i s m 235

M.C. P a t e r s o n , N.E. G e n t n e r , M V. M i d d l e s t a d t , R. M i r z a y a n s and M. W e i n f e l d

A p p l i c a t i o n o f S t a t i s t i c a l Methods to E x p e r i m e n t a l R a d i a t i o n S t u d i e s and t o R a d i a t i o n E p i d e m i o l o g y 269

A.M. K e l l e r e r

B i o l o g i c a l M o n i t o r i n g S t u d i e s i n O c c u p a t i o n a l and E n v i r o n m e n t a l H e a l t h 291

R.L. Z i e l h u i s

The R e c o g n i t i o n o f New K i n d s o f O c c u p a t i o n a l T o x i c i t y 307

J.A.H. L e e , T.L. Vaughan, P.H. D i e h r , and R.A. H a e r t l e

O c c u p a t i o n a l E x p o s u r e t o I o n i z i n g R a d i a t i o n 339 J.O. S n i h s

N o n - O c c u p a t i o n a l Exposure t o I o n i z i n g R a d i a t i o n 363 J.O. S n i h s

R i s k Assessment o f Low Doses o f R a d i a t i o n and C h e m i c a l s . . 375 R.B. S e t l o w

viii

G e n e t i c E f f e c t s o f R a d i a t i o n 383 W.J. S c h u l l

On t h e E f f e c t s o f Exposure t o Radon D a u g h t e r s i n M e t a l Mines and i n Homes 399

0. A x e l s o n

A t o m i c Bomb S u r v i v o r s : E p i d e m i o l o g y and Dose E s t i m a t i o n 413

S. J a b l o n

E p i d e m i o l o g y o f Microwave R a d i a t i o n E f f e c t s i n Humans 433

C. S i l v e r m a n

E s t a b l i s h i n g the L i n k between Human Proto-Oncogenes and Growth F a c t o r s 459

K.C. R o b b i n s , H I g a r a s h i , A. G a z i t , Ing-Ming C h i u , S.R. T r o n i c k and S.A. Aar o n s o n

Melanoma and Other S k i n C a n c e r s : A C o n t r a s t i n S o l a r R a d i a t i o n C a r c i n o g e n e s i s 471

J.A.H. Lee

E p i d e m i o l o g i c a l Approach t o B r e a s t Cancer E t i o l o g y 479 P. B r u z z i

E p i d e m i o l o g i e S t u d i e s o f C h e m o t h e r a p y - R e l a t e d A c u t e Leukemia 499

M.H. Greene

The C e n t r a l Nervous System and i n U t e r o Exposure to I o n i z i n g R a d i a t i o n : The H i r o s h i m a and N a g a s a k i E x p e r i e n c e s 515

W.J. S c h u l l and M. Otake

Unanswered I s s u e s i n Lo w - L e v e l C h e m i c a l P o l l u t i o n : The Case o f D i o x i n s and R e l a t e d Compounds 537

P. B r u z z i and P. S t r i g i n i

R a d i a t i o n E x p o s ure and L e v e l s o f O c c u p a t i o n a l S a f e t y 551

E.E. P o c h i n

Index 573

ix

FUNDAMENTALS OF DOSIMETRY AND MICRODOSIMETRY AND THE

R E L A T I V E B I O L O G I C A L E F F E C T I V E N E S S OF I O N I Z I N G RADI AT10 NS

A l b r e c h t M. K e l l e r e r I n s t i t u t für M e d i z i n i s c h e Strahlenkünde d e r Universität Würzburg V e r s b a c h e r S t r a s s e 5 D-8700 Würzburg

INTRODUCTION

The e f f e c t s of i o n i z i n g r a d i a t i o n s h a ve b e e n e x p l o r e d i n i n n u m e r a b l e b i o l o g i c a l e x p e r i m e n t s , b u t t h e y h a v e a l s o b e e n i n f l i c t e d - o f t e n w i t h t r a g i c n e g l i g e n c e or i r r e s p o n -s i b i l i t y - on human p o p u l a t i o n s . The w o r l d w i d e f a s c i n a t i o n w i t h x - r a y s i m m e d i a t e d l y a f t e r Röntgen's d i s c o v e r y was m o t i v a t e d by o p t i m i s t i c e x p e c t a t i o n s a n d p e r m i t t e d l i t t l e a t t e n t i o n t o b i o l o g i c a l damage s e e n i m m e d i a t e l y , s u c h as s k i n - l e s i o n s , o r t o t h e l a t e r o c c u r r e n c e o f l e u k e m i a s i n r a d i o 1 o g i s t s . S e v e r a l d e c a d e s a f t e r t h e i r d i s c o v e r y x - r a y s w e r e s t i l l w i d e l y a s s u m e d t o h a v e g e n e r a l p o s i t i v e e f f e c t s a n d n e a r l y u n i v e r s a l m e d i c a l a p p 1 i c a b i 1 i t y . A p a i n f u l p r o c e s s o f l e a r n i n g t h e n l e d t o t h e s t e p w i s e d e v e l o p m e n t o f a d e q u a t e r a d i a t i o n - p r o t e c t i o n p r o c e d u r e s a n d t o a more r e a l i s t i c a s s e s s m e n t of t h e b e n e f i c i a l a n d d e t r i m e n t a l p o t e n t i a l of i o n i z i n g r a d i a t i o n s . As a r e a c t i o n t o p a s t i n d u s t r i a l m i s u s e s o f r a d i o - i s o t o p e s a n d e r r o r s i n t h e i r m e d i c a l a p p l i c a t i o n one h a s , t o d a y , i n many w a y s gone t o t h e o t h e r e x t r e m e . B e y o n d t h i s , i t h a s become d i f f i c u l t , a f t e r H i r o s h i m a and N a g a s a k i , t o d r a w a r a t i o n a l ' b a l a n c e b e t w e e n t h e u s e s a nd t h e m i s u s e s o f n u c l e a r e n e r g y .

The r e s u l t i n g a t t i t u d e a n d p u b l i c p e r c e p t i o n of i o n ­i z i n g r a d i a t i o n s h as made i t d i f f i c u l t t o d i s c e r n s i m i l a r -i t i e s a n d d i s s i m i 1 a r i t i e s b e t w e e n t h e a c t i o n s of i o n i z i n g r a d i a t i o n s a n d o t h e r a g e n t s , s u c h a s c h e m i c a l c a r c i n o g e n s . I n a d i s c u s s i o n of f u n d a m e n t a l s of d o s i m e t r y a n d m i c r o -d o s i m e t r y one may, t h e r e f o r e , c o n s i d e r f i r s t p r e s u m e d o r r e a l p a r t i c u l a r i t i e s of i o n i z i n g r a d i a t i o n s a n d t h e i r

123

b i o l o g i c a l e f f e c t s w i t h some of t h e e a t t e n d a n t p r o b l e m s o g i c a l s t u d i e s , w i q u a l i t y , a n d w i t h of r a d i a t i o n s .

A b s o r b e d d o s e e n e r g y t r a n s m i t t e d e l e m e n t of m a t t e r d i s t r i b u t i o n o f ab m i c r o s c o p i c r a n d o m t h e two e s s e n t i a l of d i f f e r e n t t y p e s f o r m e r a r e t h e o b j l a t t e r t h e o b j e c t i p h y s i c s , m i c r o d o s i e r e d i t i s h e l p f u l t h e e n e r g y d e n s i e f f e c t s .

I t i s some t i me s t h o u g h t t h a t i o n i z i n 9 r a d i at i o n s p r o d -u ce s p e c i f i c d e l e t e r i o u s e f f e c t s , a n d t ha t t h ey p r od u ce them by e x t r a o r d i n a r i l y sm a 11 amo u n t s of e n e r gy Bo t h a s s u m p t i o n s a r e e r r on eou s. T h e r e i s n o e f f e c t of i on i z i n g r a d i a t i o n s t h a t ca n no t a l s o be p r o d u ce d by c hem i c a 1 C o m p o u n d s . The r e m a r k a b l e f e a t u r e o f i on i z i n 9 r a d i a t i on s i s m e r e l y t h e ex t r eme1y b r oa d s p e c t r um 0 f b i o l o g i c a 1 en d p o i n t s . The e n e r g i e s r e q u i r e d t o p r o d u c e b i o l o g i c a 1 e f f ec t s w o u l d seem t o be m i n i m a l i f c o m p a r e d t o t h e r m a l e n e r g y . A l e t h a l d o s e t o man t r a n s f e r s an e n e r g y t o t h e b o d y t h a t i n -c r e a s e s i t s t e m p e r a t u r e by l e s s t h a n 0.001 d e g r e e c e n t i -g r a d e . H o w e v e r , t h e c o m p a r i s o n t o t e m p e r a t u r e - t h e most d e g r a d e d f o r m of e n e r g y - i s m i s l e a d i n g . I t i s some w h a t more i n f o r m a t i v e t o c o n s i d e r t h e t o t a l e n e r g y c o r r e -s p o n d i n g t o a l e t h a l d o s e of 5 g r a y , w h i c h i s 350 j o u l e or 350 w a t t * s e c o n d s . An e v e n b e t t e r i l l u s t r a t i o n i s t h e c o m p a r i s o n t o m e c h a n i c a l e n e r g y . One g r a y c o r r e s p o n d s t o t h e e n e r g y r e q u i r e d t o l i f t t h e e x p o s e d o b j e c t by 0.1 m e t r e i n t h e e a r t h ' s g r a v i t a t i o n ; t h e l e t h a l d o s e c o r r e s p o n d s t o an e l e v a t i o n by 0.5 m e t r e , e v i d e n t l y s u f f i c i e n t e n e r g y t o p r o d u c e damage. V i s u a 1 i z a t i o n s of t h e e f f e c t s of i o n i z i n g r a d i a t i o n s on t h e m i c r o s c o p i c or t h e a t o m i c l e v e l c a n be s i m i l a r l y d i s p a r a t e . A t a d o s e of 1 g r a y , o n l y one o u t of t e n t o h u n d r e d b i l l i o n e l e c t r o n s i n t h e e x p o s e d m a t e r i a l i s d i s t u r b e d . On t h e o t h e r h a n d , t h e r e a r e , a t t h i s d o s e , r o u g h l y 100 000 e l e c t r o n i c d i s p l a c e m e n t s i n t h e n u c l e u s of a m a m m a l i a n c e l l .

. The s u b s e q u e n t s h o r t s u r v e y w i l l d e a l s s e n t i a l s of r a d i a t i o n p h y s i c s , w i t h t h e

i n d o s i m e t r y , p a r t i c u l a r l y i n e p i d e m i o l -t h p a r a m e t e r s t h a t c h a r a c t e r i z e r a d i a t i o n some g e n e r a l i m p l i c a t i o n s f o r t h e a c t i o n

i s - i n a s i m p l i f i e d f o r m u l a t i o n - t h e f r o m a r a d i a t i o n f i e l d t o a s m a l l

d i v i d e d by i t s mass ( 1 ) . The m a c r o s c o p i c s o r b e d d o s e i n an i r r a d i a t e d b o d y and t h e

f l u c t u a t i o n s of e n e r g y d e p o s i t i o n a r e f a c t o r s t h a t d e t e r m i n e t h e e f f e c t i v e n e s s a n d e n e r g i e s of i o n i z i n g r a d i a t i o n s . The

e c t i v e of c o n v e n t i o n a l d o s i m e t r y , t h e ve of t h e more r e c e n t b r a n c h of r a d i a t i o n m e t r y . B e f o r e t h e s e two a r e a s a r e c o n s i d -

t o i l l u s t r a t e t h e o r d e r of m a g n i t u d e of t i e s t h a t c a u s e o b s e r v a b l e b i o l o g i c a l

124

CONVENTIONAL DOSIMETRY

The M a c r o s c o p i c D i s t r i b u t i o n of E n e r g y

A l l i o n i z i n g r a d i a t i o n s w o r k u l t i m a t e l y t h r o u g h t h e a c t i o n of e l e c t r o n s . E l e c t r o n s c a n be t h e p r i m a r y r a d i a t i o n , or t h e y c a n be p r o d u c e d as s e c o n d a r y r a d i a t i o n by x - r a y s or g a m m a - r a y s . The e l e c t r o n s c a n a l s o be t h e s e c o n d a r y r a d i a t i o n p r o d u c e d a l o n g t h e t r a c k s of h e a v y c h a r g e d p a r t i c l e s . F i n a l l y t h e y c a n be t h e t e r t i a r y r a d i a t i o n o c c u r r i n g w i t h h i g h e n e r g y n e u t r o n s ; t h e y a r e t h e n r e l e a s e d by t h e h e a v y c h a r g e d r e c o i l s of t h e n e u t r o n s . I n r a d i a t i o n p r o t e c t i o n one d e a l s m o s t l y w i t h u n c h a r g e d p r i m a r i e s , i . e . w i t h x - r a y s , g a m m a - r a y s , o r n e u t r o n s , when t h e b o d y i s e x p o s e d t o e x t e r n a l s o u r c e s . C h a r g e d p r i m a r i e s a r e of c o n c e r n m o s t l y i n c o n n e c t i o n w i t h i n t e r n a l e m i t t e r s .

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The d o s i m e t r y o f i o n i z i n g r a d i a t i o n s i s n e v e r t r i v i a l when one i s c o n c e r n e d w i t h l a r g e e x p o s e d o b j e c t s , s u c h as t h e human b o d y . W i t h e n e r g e t i c p h o t o n s or n e u t r o n s b e y o n d 20 MeV t h e t o t a l b o d y i r r a d i a t i o n may be n e a r l y u n i f o r m . H o w e v e r , f o r t h e s e v e r y e n e r g e t i c r a d i a t i o n s c r o s s -s e c t i o n s , a n d s p e c i f i c a l l y t h e n u c l e a r c r o s s - s e c t i o n s , a r e s t i l l i n a d e q u a t e l y k n o w n . A t t h e more common i n t e r m e d i a t e e n e r g i e s , i n t h e ränge o f 0.1 t o 20 MeV, t h e c r o s s - s e c t i o n s a r e a d e q u a t e l y k n o w n , b u t t h e p e n e t r a t i o n of t h e r a d i a t i o n i s t h e n l i m i t e d , a n d d o s e d i s t r i b u t i o n s i n an e x p o s e d b o d y a r e c o m p l e x a n d d e p e n d on n u m e r o u s p a r a m e t e r s .

F i g . l g i v e s f o r u n c h a r g e d a n d f o r c h a r g e d p a r t i c l e s t h e i r mean f r e e p a t h a n d t h e i r ränge f o r e n e r g i e s b e t w e e n 10 keV a n d 10 MeV. The e s s e n t i a l O b s e r v a t i o n i s , t h a t t h e mean f r e e p a t h o f t h e u n c h a r g e d p a r t i c l e s i s a l w a y s c o n s i d -e r a b l y l a r g e r t h a n t h e r a n g e s of t h e c h a r g e d s e c o n d a r i e s . F o r many p u r p o s e s one c a n , t h e r e f o r e , s i m p l i f y d o s i m e t r i c c o m p u t a t i o n s by n e g l e c t i n g e n e r g y t r a n s p o r t by t h e c h a r g e d s e c o n d a r i e s . W i t h t h i s s i m p 1 i f i c a t i o n one o b t a i n s t h e q u a n t i t y k e r m a ( K i n e t i c E n e r g y R e l e a s e d i n M A t t e r ) i n s t e a d of a b s o r b e d d o s e . I t i s e v i d e n t t h a t k e r m a and a b s o r b e d d o s e c a n be u s e d i n t e r c h a n g e a b 1 y i f , i n a s p e c i f i e d g e o m e t r y , a l l d i m e n s i o n s of i n t e r e s t e x c e e d t h e maximum r a n g e s of c h a r g e d p a r t i c l e s . I f t h i s c o n d i t i o n i s n o t f u l f i l l e d , one must a c c o u n t f o r t h e d i f f e r e n t s p a t i a l d i s t r i b u t i o n s of t h e two q u a n t i t i e s . A b s o r b e d d o s e i n c l u d e s a f u r t h e r d e g r a d a t i o n p r o c e s s ; t h e g r a d i e n t s of a b s o r b e d d o s e a r e t h e r e f o r e a l w a y s l e s s t h a n t h o s e of k e r m a .

B e y o n d t h e f a c i l i t a t i o n of c o m p u t a t i o n s , t h e c o n c e p t of k e r m a p e r m i t s a f u r t h e r s i m p l i f i c a t i o n . K e r m a f o r a n y s p e c i f i e d m a t e r i a l i s d e f i n e d e v e n i n a r e c e p t o r f r e e geom­e t r y , e . g . i n f r e e S p a c e . A s i m i l a r p o s s i b i l i t y d o e s n o t e x i s t f o r a b s o r b e d d o s e , w h i c h i s a l w a y s a c o m p l e x r e s u l t of a t t e n u a t i o n a n d b a c k s c a t t e r , a n d of t h e b u i l d - u p o f c h a r g e d p a r t i c l e e q u i l i b r i u m i n a s p e c i f i e d g e o m e t r y . T h e s e c o m p l e x i t i e s of a b s o r b e d d o s e a r e s o m e t i m e s d i s r e g a r d e d w i t h t h e s i l e n t a s s u m p t i o n of a r e f e r e n c e v o l u m e l a r g e e n o u g h t o a t t a i n c h a r g e d p a r t i c l e e q u i l i b r i u m b u t s m a l l e n o u g h t h a t a t t e n u a t i o n a n d b a c k s c a t t e r c a n be d i s r e ­g a r d e d . F o r c r u d e e s t i m a t e s t h i s may be an a d m i s s a b l e p r o c e d u r e . I n r i g o r o u s S t a t e m e n t s t h e r e f e r e n c e t o a b s o r b e d d o s e w i t h o u t s p e c i f i e d g e o m e t r y must be a v o i d e d . F i g . l i l l u s t r a t e s t h e d i f f i c u l t y by s h o w i n g t h a t t h e r a n g e s of th e r e l e a s e d e l e c t r o n s c a n , a t h i g h e n e r g i e s , be e q u a l t o s e v e r a l p e r c e n t of t h e mean f r e e p a t h of p h o t o n s .

A l t h o u g h t h e u s e of e x p o s u r e a n d i t s u n i t s röntgen o r C/kg i s now d i s c o u r a g e d one may n o t e t h a t t h i s q u a n t i t y ,

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t o o , i s d e f i n e d r e g a r d l e s s of e n e r g y t r a n s p o r t by c h a r g e d p a r t i c l e s , a n d t h a t i t i s , t h e r e f o r e , d e f i n e d e v e n i n r e -c e p t o r f r e e c o n d i t i o n s .

F o r d o s e p l a n n i n g a n d d o s e a s s e s s m e n t i n r a d i o t h e r a p y i n a c c u r a c i e s must n o t e x c e e d a few p e r c e n t . P r e c i s e m e a s u r e m e n t s a nd a c c u r a t e c o m p u t a t i o n s a r e t h u s r e q u i r e d . S i m i l a r r e q u i r e m e n t s f o r d o s e s p e c i f i c a t i o n c a n be met i n many r a d i o b i o 1 o g i c a 1 s t u d i e s , e i t h e r w i t h c e l l c u l t u r e s o r w i t h s m a l l l a b o r a t o r y a n i m a l s . I n e p i d e m i o l o g i c a l s t u d i e s t h e i n a c c u r a c i e s a r e f a r g r e a t e r a n d f a r more c o m p l e x .

The d i f f i c u l t i e s a n d c o m p l e x i t i e s of t h e d o s i m e t r i c P r o b l e m s a r e e x e m p l i f i e d by t h e s t u d i e s on t h e a t o m i c bomb s u r v i v e r s . The c u r r e n t r e e v a l u a t i o n of t h e d o s i m e t r y h a s b e e n n e c e s s i t a t e d by i n a c c u r a c i e s o f t h e i n p u t d a t a f o r t h e t e n t a t i v e Oak R i d g e d o s i m e t r y o f 1 9 6 5 (TD 6 5 ) . T h e r e w e r e u n c e r t a i n t i e s c o n c e r n i n g t h e y i e l d s a n d t h e e n e r g y s p e c t r a o f t h e n e u t r o n s a n d t h e g a m m a - r a y s as w e l l as t h e g e o m e t r y of t h e bomb a s s e m b l i e s a n d t h e h u m i d i t y o f t h e a t m o s p h e r e a t t h e t i m e of t h e b o m b i n g s . I m p r o v e m e n t s i n t h e t r a n s p o r t c o d e s , p a r t i c u l a r l y f o r n e u t r o n s , a r e e q u a l l y i m p o r t a n t . As a r e s u l t t h e t i s s u e - k e r m a v a l u e s i n a i r h a v e b e e n s u b s t a n t i a 1 1 y c h a n g e d . H o w e v e r , a s a new c o n s e n s u s on t h e d o s i m e t r y a p p e a r s t o e m e r g e t h e r e r e m a i n l a r g e a r e a s of u n c e r t a i n t y . P e r h a p s most i m p o r t a n t l y , new i n d i v i d u a l s h i e l d i n g f a c t o r s r e m a i n t o be e s t a b l i s h e d . T h e f r e e a i r k e r m a s h a v e t o be r e d u c e d t o k e r m a s i n t h e b u i l d i n g s w h e r e i n d i v i d u a l s w e r e a t t h e t i m e of t h e b o m b i n g ; t h e r e d u c t i o n c a n be a p p r e c i a b l e a n d i t d e p e n d s s t r o n g l y on e n e r g y . The f u r t h e r r e d u c t i o n f r o m k e r m a w i t h i n t h e b u i l d i n g t o o r g a n d o s e s i s a l s o s u b s t a n t i a l . F o r t h e d e e p e r o r g a n s t h e r e d u c t i o n f a c t o r s a r e 0.7 t o 0.85 f o r g a m m a - r a y s , a n d 0.1 t o 0.2 f o r n e u t r o n s ( 2 , 3 ) . F o r t h e s u p e r f i c i a l o r g a n s , s u c h as t h e b r e a s t s , t h e r e i s t h e a d d i t i o n a l c o m p l e x i t y o f a d e p e n d e n c e on t h e o r i e n t a t i o n o f t h e p e r s o n a t t h e t i m e o f t h e e x p l o s i o n a n d d u r i n g t h e s u b s e q u e n t s e c o n d s of d e l a y e d i r r a d i a t i o n .

The r e l a t i v e c o n t r i b u t i o n s t i l l i n a d e q u a t e l y k n o w n . So f r o m f a l l - o u t , i n c l u d i n g t h e p b l a c k r a i n .

of t h e d e l a y e d r a d i a t i o n i s a r e p o s s i b l e c o n t r i b u t i o n s

o s s i b l e r o l e of t h e s o - c a l l e d

I t i s c h a r a c t e r i s t i c f o r r a d i a t i o n e p i d e m i o l o g y t h a t t h e d o s i m e t r i c p r o b l e m s a r e f u r t h e r c o m p l i c a t e d by f a r l e s s t a n g i b l e u n c e r t a i n t i e s . R u l e s of c o m p e n s a t i o n a n d m e d i c a l c a r e f o r t h e a t o m i c bomb s u r v i v e r s w e r e p a r t l y d e p e n d e n t on d o s e r e c e i v e d ; t h e y may t h e r e f o r e h a v e i n f l u e n c e d t h e S t a t e m e n t s of i n d i v i d u a l s c o n c e r n i n g t h e i r l o c a l i z a t i o n a t

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t h e t i m e of t h e b l a s t s . T h e r e c o u l d a l s o h a v e b e e n an o p p o s i t e e f f e c t due t o t h e d e s i r e t o a v o i d any s o c i a l s t i g m a l i n k e d t o h e a v y e x p o s u r e . To name s t i l l a n o t h e r p o s s i b l e d i f f i c u l t y , t h e r e had b e e n s e v e r e s h o r t a g e s o f x -r a y f i l m s i n t h e p e r i o d a f t e r t h e b o m b i n g , a n d t h i s may h a v e l e d t o e x t e n s i v e u s e of f l u o r o s c o p y a n d t h u s t o r a d i a t i o n d o s e s i n a d d i t i o n t o t h o s e f r o m t h e bomb.

The d o s i m e t r i c s t u d i e s f o r H i r o s h i m a a nd N a g a s a k i h a v e b e e n r e f e r r e d t o as e x a m p l e s of d i f f i c u l t a n d p a r t l y u n r e -s o l v e d p r o b l e m s i n r a d i a t i o n e p i d e m i o l o g y . The same s t u d i e s a r e , h o w e v e r , a l s o e x e m p l a r y a n d i m p r e s s i v e e f f o r t s . S u c h e f f o r t s m u st c o n t i n u e , b e c a u s e t h e v a r i o u s c o l l e c t i v e s of s u b s t a n t i a l l y e x p o s e d p e r s o n s a r e u n i q u e and w i l l , h o p e -f u l l y , r e m a i n s o .

The n u m e r o u s i n v e s t i g a t i o n s of t h e e f f e c t s of i n t e r n a l e m i t t e r s p o s e p r o b l e m s of c o m p a r a b l e o r e v e n h i g h e r c o m p l e x i t y ( s e e f o r e x a m p l e ( 4 ) ) . I n t e r n a l e m i t t e r s p r o d u c e - w i t h few e x c e p t i o n s s u c h a s t r i t i u m - h i g h l y n o n - u n i f o r m e x p o s u r e s . F o r e x a m p l e i n p a t i e n t s t h a t h a v e b e e n e x p o s e d t o t h e s h o r t l i v e d r a d i u m - 2 2 4 by f a r t h e l a r g e s t d o s e s w e r e p r o d u c e d i n n a r r o w r e g i o n s on t h e b o n e s u r f a c e s ( 5 ) . S t i l l f u r t h e r c o m p l e x i t i e s o c c u r w i t h i n h a l e d a c t i v i t y s u c h as r a d o n d a u g h t e r s . The s t u d y o f t h e d i s t r i b u t i o n of t h e r a d o n d a u g h t e r s i n d i f f e r e n t a r e a s o f t h e l u n g i s , by i t s e l f , a s p e c i a l i z e d f i e l d of i n q u i e r y , as i s t h e i n v e s t i g a t i o n of t h e d o s e d e p e n d e n c e a n d t h e g e o m e t r i c a n d t e m p o r a l d i s t r i b u t i o n of l u n g t u m o r s i n d u c e d by t h e i n h a l e d a c t i v i t y .

The m i c r o d i s t r i b u t i o n of a b s o r b e d d o s e i n t h e v i c i n i t y of p a r t i c u l a t e a 1 p h a - e m i 1 1 e r s i n t h e l u n g i s an a d d i t i o n a l c o m p l e x i t y of i n h a l a t i o n s t u d i e s . T h i s h o t s p o t p r o b lern e x e m p l i f i e s f u r t h e r t h e w i d e ränge o f d o s i m e t r i c p r o b l e m s , a n d p o s e s p r o b l e m s i n t e r m e d i a t e b e t w e e n c o n v e n t i o n a l d o s i m e t r y a n d m i c r o d o s i m e t r y ( 6 ) ; i t r e a c h e s b e y o n d t h e s c o p e of t h i s s u r v e y .

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MICRODOSIMETRY

The M i c r o s c o p i c D i s t r i b u t i o n of E n e r g y

A b s o r b e d d o s e i s d e f i n e d i n t e r m s of t h e e x p e c t e d v a l u e of t h e e n e r g y t r a n s f e r r e d by i o n i z i n g r a d i a t i o n t o a mass e l e m e n t . I t i s , a c c o r d i n g l y , a S t a t i s t i c a l c o n c e p t t h a t l o s e s a p p 1 i c a b i 1 i t y when one d e a l s w i t h s m a l l d o s e s , w i t h s m a l l s t r u c t u r e s , a n d , e s p e c i a l l y , w i t h d e n s i l y i o n i z i n g r a d i a t i o n s . The m i c r o s c o p i c f l u c t u a t i o n s o f e n e r g y d e p o s i t i o n c a n t h e n be c o n s i d e r a b 1 e . F i g . 2 i n d i c a t e s , f o r s p a r s e l y a n d f o r d e n s e l y i o n i z i n g r a d i a t i o n s , t h e s i z e s of s p h e r i c a l r e g i o n s i n t i s s u e a n d t h e d o s e s w h e r e t h e S t a n d a r d d e v i a t i o n s of e n e r g y d e p o s i t i o n e x c e e d 2 0 % .

ABSORBED DOSE / Gy F i g . 2 . The s h a d e d a r e a s i n d i c a t e t h o s e c o m b i n a t i o n s of s i t e s i z e s a n d a b s o r b e d d o s e s w h e r e t h e S t a n d a r d d e ­v i a t i o n s of e n e r g y i m p a r t e d e x c e e d 2 0 % . A b s o r b e d d o s e c a n t h e n n o t be a p p l i e d n a i v e l y , a n d a t r e a t m e n t i n t e r m s of m i c r o d o s i m e t r y i s r e q u i r e d .

The f i g u r e i s b a s e d on m i c r o d o s i m e t r i c c o m p u t a t i o n s a n d m e a s u r e m e n t s , b u t i t s m e a n i n g c a n be u n d e r s t o o d e v e n b e f o r e t h e p r i n c i p l e s of m i c r o d o s i m e t r y a r e f o r m a l l y i n t r o d u c e d . A t d o s e s of s e v e r a l mGy, i . e . a t t h e l e v e l o f r a d i a t i o n p r o t e c t i o n , t h e a b s o r b e d d o s e i s n e v e r m e a n i n g f u l , e v e n i f t h e e n t i r e n u c l e u s of t h e c e l l o r t h e c e l l i t s e l f i s c o n -

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s i d e r e d . M o s t c e l l s r e c e i v e , i n t h i s d o s e ränge, no e n e r g y d e p o s i t i o n a t a l l ; t h o s e c e l l s t h a t a r e t r a v e r s e d by a c h a r g e d p a r t i c l e r e c e i v e e n e r g i e s t h a t c a n be f a r i n e x c e s s of t h e e x p e c t a t i o n v a l u e c o r r e s p o n d i n g t o a b s o r b e d d o s e . A l t h o u g h t h e a f f e c t e d c e l l s a r e o n l y a m i n o r f r a c t i o n of a l l c e l l s , t h e i r t o t a l number i s , of c o u r s e , v e r y l a r g e . The i m p o r t a n t c o n s e q u e n c e of t h i s b a s i c f e a t u r e of i o n i z i n g r a d i a t i o n s i s t h a t no t h r e s h o l d i n a b s o r b e d d o s e c a n h o l d f o r c e l l u l a r e f f e c t s . F o r s m a l l e r c e l l s t r u c t u r e s , s u c h as i n d i v i d u a l c h r o m o s o m e s , t h e d o s e c o n c e p t r e m a i n s i n a p p l i ­c a b l e e v e n a t t h e h i g h e s t d o s e s of b i o l o g i c a l i n t e r e s t .

The d i s c o n t i n u o u s e n e r g y t r a n s f e r by i o n i z i n g r a d i a t i o n s h a s a t t r a c t e d a t t e n t i o n e a r l y i n t h e d e v e l o p m e n t of r a d i a t i o n b i o l o g y . I t has l e d t o t h e h i t and t a r g e t t h e o r i e s ( f o r s u r v e y s s e e ( 7 - 9 ) ) . S u c h t h e o r i e s , a l t h o u g h t h e y w e r e v a l i d as h e u r i s t i c p r i n c i p l e s , h a v e h a d o n l y l i m i t e d p r a g m a t i c s u c c e s s . T h e y w e r e b a s e d on t h e p o s t u l a t e o f e q u a l a n d s t a t i s t i c a 1 l y i n d e p e n d e n t h i t p r o c e s s e s a n d of h y p o t h e t i c a l c e l l u l a r t a r g e t s w h i c h h a v e n e v e r b e e n i d e n t i f i e d . A m o r e s u c c e s s f u l a p p r o a c h r e q u i r e s r e a l i s t i c p h y s i c a l p a r a m e t e r s of r a d i a t i o n q u a l i t y . The most s i m p l i f i e d , b u t s t i l l t h e most common, p a r a m e t e r i s l i n e a r e n e r g y t r a n s f e r ( L E T ) , a l s o c a l l e d c o l l i s i o n s t o p p i n g p o w e r , of c h a r g e d p a r t i c l e s . I t c h a r a c t e r i z e s t h e a v e r a g e l o c a l c o n c e n t r a t i o n of e n e r g y a l o n g t h e t r a c k o f a c h a r g e d p a r t i c l e , a n d i t i s s t i l l t h e p a r a m e t e r t h a t d e t e r m i n e s t h e q u a l i t y f a c t o r e m p l o y e d i n r a d i a t i o n p r o t e c t i o n ( 1 0 ) . H o w e v e r , L E T i t s e l f i s m e r e l y a S t a t i s t i c a l e x p e c t a t i o n v a l u e . E n e r g y - l o s s s t r a g g l i n g , t h e r a d i a l t r a n s p o r t of e n e r g y away f r o m t h e p a r t i c l e t r a c k by d e l t a - r a y s , a n d t h e c h a n g e o f LET a l o n g t h e p a r t i c l e t r a j e c t o r y a r e f a c t o r s t h a t c o - d e t e r m i n e a c t u a l m i c r o s c o p i c c o n c e n t r a t i o n s of e n e r g y . F o r h e a v y i o n s t h e r e a r e c o n d i t i o n s w h e r e L E T and i t s p r o b a b i l i t y d i s t r i b u t i o n s p e r m i t a d e q u a t e e s t i m a t e s of e n e r g y t r a n s f e r by i n d i v i d u a l c h a r g e d p a r t i c l e s t o t h e n u c l e u s of t h e c e l l o r c o m p a r a b l e s i t e s . F o r e l e c t r o n s t h e LET c o n c e p t i s n e v e r a d e q u a t e ( 1 1 ) .

The s h o r t c o m i n g s of t h e LET c o n c e p t h a v e b e e n r e s p o n -s i b l e f o r t h e d e v e l o p m e n t of a new b r a n c h of r a d i a t i o n p h y s i c s . When H . H . R o s s i a t t e m p t e d t o d e t e r m i n e t h e L E T d i s ­t r i b u t i o n of t h e r e c o i l s p r o d u c e d by h i g h e n e r g y n e u t r o n s he f o u n d t h a t t h e s e d i s t r i b u t i o n s w e r e n o t d i r e c t l y m e a s u r -a b l e . He t h e n r e c o g n i z e d t h a t t h e s e e m i n g l y i n a d e q u a t e r e ­s p o n s e of t h e p r o p o r t i o n a l c o u n t e r s w a s , i n f a c t , more m e a n i n g f u l t h a n t h e t h e o r e t i c a l L ET v a l u e s . The s p h e r i c a l p r o p o r t i o n a l c o u n t e r s - now known as R o s s i c o u n t e r s r e s p o n d t o e n e r g y a c t u a l l y i m p a r t e d t o t h e i r g a s v o l u m e w h i c h s i m u l a t e s a m i c r o s c o p i c t i s s u e r e g i o n . The b a s i c

130

p r i n c i p l e of m i c r o d o s i m e t r y i s t h a t c e l l u l a r e f f e c t s a r e d e t e r m i n e d by a c t u a l e n e r g y c o n c e n t r a t i o n s , n o t by t h e i r e x p e c t a t i o n v a l u e s . When t h i s s i m p l e b u t f u n d a m e n t a l p r i n c i p l e was u n d e r s t o o d ( 1 2 ) , t h e s u b s e q u e n t s t e p s f o l l o w e d of n e c e s s i t y . A c o n c e p t i o n a l f r a m e w o r k of m i e r o d o s i m e t r y was e s t a b l i s h e d a n d s u i t a b l e e x p e r i m e n t a l t e c h n i q u e s w e r e d e v e l o p e d t h a t c o u l d be a p p l i e d t o any r a d i a t i o n f i e l d t o d e t e r m i n e t h e p r o b a b i l i t y d i s t r i b u t i o n s o f e n e r g y c o n c e n t r a t i o n s on t h e m i c r o s c o p i c s c a l e ( 1 3 - 1 5 ) .

T h e r e a r e a number of c l o s e l y i n t e r r e l a t e d m i c r o d o s i m e t r i c q u a n t i t i e s :

The e n e r g y i m p a r t e d , e, i s t h e r a d i a t i o n e n e r g y t r a n s ­f e r r e d t o a g i v e n r e f e r e n c e v o l u m e o f m a t t e r .

The s p e c i f i c e n e r g y , z, i s t h e e n e r g y i m p a r t e d , as d e f i n e d a b o v e , d i v i d e d by t h e m a s s , m, of t h e r e f e r e n c e v o l u m e of m a t t e r :

z = e/m

The l i n e a l e n e r g y , y, i s t h e e n e r g y i m p a r t e d , as d e f i n e d a b o v e , d i v i d e d by t h e mean c h o r d l e n g t h , 1, r e s u l t i n g i n s t r a i g h t r a n d o m t r a v e r s a l s of t h e r e f e r e n c e v o l u m e *) :

y = e/1

The s p e c i f i c e n e r g y , z , i s t h e r a n d o m v a r i a b l e c o r -r e s p o n d i n g t o t h e n o n - s t o c h a s t i c q u a n t i t y a b s o r b e d d o s e , D. The l i n e a r e n e r g y , y, r e l a t e s o n l y t o i n d i v i d u a l e n e r g y d e p o s i t i o n e v e n t s ( i . e . i n d i v i d u a l c h a r g e d p a r t i c l e s ) , i t i s t h e s t o c h a s t i c c o u n t e r p a r t of t h e n o n - s t o c h a s t i c q u a n t i t y L E T . I n v i e w of t h e s i m p l e r e l a t i o n b e t w e e n z and y, i t i s u s u a l l y s u f f i c i e n t t o u s e t h e s p e c i f i c e n e r g y , z, as w i l l be d o n e b e l o w .

* ) I f t h e r e f e r e n c e v o l u m e i s a mean c h o r d l e n g t h i s 1 = 2d/3 mean c h o r d l e n g t h i s e q u a l t o by t h e s u r f a c e ( 1 6 ) .

s p h e r e of t h e d i a m e t e r d, t h e . F o r any c o n v e x v o l u m e t h e f o u r t i m e s t h e v o l u m e d i v i d e d

131

4 0 0 0 s i m u l a t i o n s a r e p e r f o r m e d p e r d e c a d e of d o s e f o r e a c h g r a p h . The d e c r e a s i n g number o f p o i n t s a t l o w d o s e i s due t o t h e i n c r e a s i n g number of e v e n t s w i t h z e r o s p e c i f i c e n e r g y .

15 MeV NEUTRONS .5 Hm SPHERE 15 MeV NEUTHONS 6 Mm SPHERE

10"4 10"? 5 100 10"4 10~? 1 100 ABSORBED DOSE /Gy ABSORBED DOSE /Gy

F i g . 3 . S c a t t e r d i a g r a m s of t h e d i s t r i b u t i o n of s p e c i f i c e n e r g y i n s m a l l a n d l a r g e s i t e s a n d f o r s p a r s e l y a n d d e n s e l y i o n i z i n g r a d i a t i o n .

132

A d e f i n i t e v a l u e of t h e s p e c i f i c e n e r g y c a n n o t be p r e d i c t e d f o r a m i c r o s c o p i c v o l u m e , e v e n u n d e r f u l l y d e f i n e d i r r a d i a t i o n c o n d i t i o n s . I n s t e a d t h e p o s s i b l e v a l u e s o f t h e s p e c i f i c e n e r g y a r e d e s c r i b e d by a p r o b a b i l i t y d e n s i t y , f ( z ; D ) . The o b j e c t i v e of m i c r o d o s i m e t r y i s t h e c a l c u l a t i o n or t h e e x p e r i m e n t a l d e t e r m i n a t i o n of t h e p r o b a b i l i t y d e n s i t i e s of t h e s p e c i f i c e n e r g y f o r v a r i o u s t y p e s of r a d i a t i o n a n d s p e c i f i e d r e f e r e n c e v o l u m e s . The e x p e r i m e n t a l d e t e r m i n a t i o n s a r e c a r r i e d o u t n o t d i r e c t l y i n s o l i d m a t e r i a l , b u t i n t i s s u e e q u i v a l e n t g a s v o l u m e s s i m u l a t i n g m i c r o s c o p i c r e g i o n s i n t i s s u e . W i t h o u t g o i n g i n t o t h e t e c h n i c a l d e t a i l s o f t h e c o n s t r u c t i o n of t h e R o s s i c o u n t e r s i t i s s u f f i c i e n t t o n o t e t h a t t h e i n s t r u m e n t s c a n be u s e d f o r m e a s u r e m e n t s i n a w i d e v a r i e t y o f r a d i a t i o n f i e l d s . I t i s p o s s i b l e t o s i m u l a t e t i s s u e r e g i o n s down t o a d i a m e t e r of a b o u t 0.3 m i c r o m e t e r . M i c r o d o s i m e t r i c d a t a f o r much s m a l l e r r e g i o n s a r e a l s o of c o n s i d e r a b l e i n t e r e s t , b u t t h e y h a v e t o be o b t a i n e d by c o m p u t a t i o n s . E x p e r i m e n t a l t e c h n i q u e s t o d e t e r m i n e s u c h d a t a h a v e n o t , as y e t , b e e n d e v e l o p e d .

I t i s n o t n e c e s s a r y t o m e a s u r e t h e s p e c t r a of z f o r d i f f e r e n t v a l u e s o f t h e a b s o r b e d d o s e . I n s t e a d i t i s s u f f i c i e n t t o d e t e r m i n e t h e s i n g l e - e v e n t s p e c t r a , f ( z ) , i . e . t h e d e n s i t i e s of t h e i n c r e m e n t s of t h e s p e c i f i c e n e r g y due t o S i n g l e c h a r g e d p a r t i c l e s i n c l u d i n g t h e i r s e c o n d a r i e s . I f t h e s i n g l e - e v e n t s p e c t r u m i s kno w n , i t i s p o s s i b l e t o c a l c u l a t e t h e d o s e d e p e n d e n t s p e c t r a as S o l u t i o n s o f a Compound P o i s s o n p r o c e s s ( 1 7 ) . F i g . 3 i l l u s t r a t e s , i n t h e f o r m of s c a t t e r d i a g r a m s , t h e d i s t r i b u t i o n s o f s p e c i f i c e n e r g y f o r a d e n s e l y i o n i z i n g a n d a s p a r s e l y i o n i z i n g r a d i a t i o n a n d f o r S i t e s of 0.5 a n d of 6 m i c r o m e t e r d i a m e t e r . T h e s e d i a g r a m s i l l u s t r a t e t h e l a r g e f l u c t u a t i o n s of s p e c i f i c e n e r g y ; t h e y a l s o show, by t h e a b s e n c e of p o i n t s a t s m a l l d o s e s , t h e i n c r e a s i n g p r o b a b i l t i e s f o r no e n e r g y d e p o s i t i o n .

I n most a p p l i c a t i o n s of m i c r o d o s i m e t r y t o r a d i o b i o l o g y a n d t o r a d i a t i o n p r o t e c t i o n i t i s n o t a c t u a l l y r e q u i r e d t o u t i l i z e t h e d o s e d e p e n d e n t d i s t r i b u t i o n s of s p e c i f i c e n e r ­g y . I m p o r t a n t c o n c l u s i o n s c a n , i n s t e a d , be b a s e d d i r e c t l y on t h e s i n g l e - e v e n t s p e c t r a a n d t h e i r m o m e n t s .

T y p i c a l e x a m p l e s of s i n g l e - e v e n t d i s t r i b u t i o n s a r e shown i n F i g . 4 . T h e s e s p e c t r a r e l a t e t o s p h e r i c a l t i s s u e r e g i o n s of 1 m i c r o m e t e r d i a m e t e r . The p r o n o u n c e d d i f f e r e n c e s b e t w e e n s p a r s e l y i o n i z i n g a n d d e n s e l y i o n i z i n g r a d i a t i o n s a r e e v i d e n t , b u t t h e v e r y w i d e ränge of v a l u e s o f z f o r t h e d i f f e r e n t r a d i a t i o n t y p e s a r e e q u a l l y n o t a b l e . T h e y e x t e n d o v e r s e v e r a l o r d e r s of m a g n i t u d e , i . e . a

133

d e n s e l y i o n i z i n g r a d i a t i o n c a n a l w a y s p r o d u c e e v e n t s w i t h r e l a t i v e l y s m a l l e n e r g y d e p o s i t i o n , a n d , v i c e v e r s a , m o d e r a t e t o h i g h v a l u e s of z o c c u r e v e n w i t h s p a r s e l y i o n i z i n g r a d i a t i o n s . T h e r e i s , a c c o r d i n g l y , no s h a r p d i v i d i n g l i n e b e t w e e n d e n s e l y i o n i z i n g and s p a r s e l y i o n i z i n g r a d i a t i o n s .

1 zd(z) y d(y)

.01

.01 z/Gy

10 - 1 —

100

y r o y s 14.7 M e V n e u t r o n s

2 5 0 k V p x - r o y s 3.7 MeV n e u t r o n s

1 10 y/ keV/^jm

100 1000

F i g . 4 . S i n g l e e v e n t d i s t r i b u t i o n s of s p e c i f i c e n e r g y a n d l i n e a l e n e r g y f o r a s p h e r i c a l t i s s u e r e g i o n of 1 m i c r o ­m e t e r d i a m e t e r . D i s t r i b u t i o n s of d o s e , r a t h e r t h a n e v e n t n u m b e r s , a r e g i v e n r e l a t i v e t o t h e l o g a r i t h m i c s c a l e ( 1 8 ) .

The l a r g e r t h e i n c r e m e n t s of s p e c i f i c e n e r g y p e r e v e n t , t h e s m a l l e r i s t h e mean number o f e v e n t s p e r u n i t of a b s o r b e d d o s e . T a b l e 1 shows e v e n t f r e q u e n c i e s f o r v a r i o u s t y p e s of r a d i a t i o n . F i g . 5 i n d i c a t e s , l a r g e l y i n a n a l o g y t o F i g . 2 , t h o s e s i t e s i z e s and d o s e s w h e r e t h e mean e v e n t f r e q u e n c y i s l e s s t h a n 1. T h e s e d a t a p e r m i t i m p o r t a n t c o n c l u s i o n s . I n p a r t i c u l a r , d o s e - e f f e c t r e l a t i o n s must a l w a y s be l i n e a r when t h e mean e v e n t number i n t h e c e l l o r i n t h e s e n s i t i v e c e l l o r g a n e l l e s i s much s m a l l e r t h a n 1. W i t h d e n s e l y i o n i z i n g r a d i a t i o n t h i s c o n d i t i o n i s met e v e n a t d o s e s of t h e o r d e r of s e v e r a l g r a y . H o w e v e r , t h e a r g u m e n t a p p l i e s o n l y t o d o s e - e f f e c t r e l a t i o n s f o r a u t o n o m o u s c e l l s , i . e . t o c e l l s t h a t a r e n o t i n f l u e n c e d by e n e r g y d e p o s i t i o n i n a d j a c e n t c e l l s o r by r a d i a t i o n i n d u c e d r e a c t i o n s of t h e t i s s u e ( 2 2 ) .

134

The p o s t u l a t e of r a d i a t i o n a c t i o n on a u t o n o m o u s c e l l s a p p e a r s t o a p p l y t o h e r e d i t a r y e f f e c t s w h i c h a r e due t o

T a b l e 1: E v e n t f r e q u e n c i e s i n s p h e r i c a l t i s s u e r e g i o n s of s p e c i f i e d d i a m e t e r .

TYPE OF RADIATION

SITE

DIAMETER

(pm)

^ ° C o - Y - R a d i a t i o n

* (Gy"')

NEUTRONS

• ( G y "1

)

.A3 MeV 5.7 MeV 15 MeV

12 2000 55 51 61 5 360 k.2 8.6 11 2 58 .39 1.2 1.6

1 12 .08 • 32 .38

.5 1.7 .02 .07 .09

ABSORBED DOSE / Gy F i g . 5 . The s h a d e d a r e a s i n d i c a t e c o m b i n a t i o n s of s i t e s i z e s and a b s o r b e d d o s e s w h e r e t h e e x p e c t e d number of e n e r g y d e p o s i t i o n e v e n t s i s l e s s t h a n 1, and d o s e d e p e n d e n c e s -f o r a u t o n o m o u s r e s p o n s e - must a c c o r d i n g l y by l i n e a r .

135

m u t a t i o n s or c h r o m o s o m e a b e r r a t i o n s i n i n d i v i d u a l c e l l s . I t i s f a r l e s s c e r t a i n when a p p l i e d t o r a d i a t i o n c a r c i n o ­g e n e s i s . I n f a c t , n o n - l i n e a r d o s e - e f f e c t r e l a t i o n s h a v e b e e n f o u n d a t n e u t r o n d o s e s f a r t o o s m a l l f o r an a p p r e c i a b l e p r o b a b i l i t y of m u l t i p l e e v e n t s i n t h e c e l l ( 1 9 -2 1 ) . One must c o n c l u d e t h a t r a d i a t i o n t u m o r i g e n e s i s i s c o -d e t e r m i n e d by d o s e d e p e n d e n t t i s s u e f a c t o r s t h a t a r e , as y e t , u n r e s o l v e d . L i n e a r i t y a t l o w d o s e s r e m a i n s , t h e r e f o r e , a mere h y p o t h e s i s f o r r a d i a t i o n c a r c i n o g e n e s i s .

I M P L I C A T I O N S FOR R A D I A T I O N PROTECTION

D o s i m e t r y

A b s o r b e d d o s e a n d t h e r e l a t e d q u a n t i t y d o s e e q u i v a l e n t a r e u t i l i z e d i n t h e l i m i t a t i o n p r i n c i p l e o f r a d i a t i o n p r o t e c t i o n . T h i s p r i n c i p l e i s b a s e d on a n n u a l d o s e -e q u i v a l e n t l i m i t s w h i c h o b v i a t e t h e n e e d t o r e t a i n I n f o r m a t i o n on e x p o s u r e s of i n d i v i d u a l s i n e a r l i e r c a l e n d a r y e a r s . A n o t h e r c o n v e n i e n c e has b e e n - up t o a r e c e n t c h a n g e - t h a t t h e maximum d o s e e q u i v a l e n t i n any o r g a n r a t h e r t h a n a more c o m p l e x q u a n t i t y h a s b e e n l i m i t e d . A f u r t h e r f e a t u r e of t h e l i m i t S y s t e m i s t h e a b s e n c e of any h y p o t h e s i s c o n c e r n i n g t h e f o r m of t h e d o s e - e f f e c t r e l a t i o n s .

H o w e v e r , t h e r e has b e e n i n p a s t y e a r s a g r a d u a l c h a n g e away f r o m t h e l i m i t t o t h e a s s e s s m e n t S y s t e m . H . H . R o s s i ha s r e c e n t l y a n a l y s e d t h e c h a n g e and i t s c o n s e q u e n c e s i n d e p t h ( 2 2 ) , and o n l y some o f t h e e s s e n t i a l s w i l l be c o n s i d e r e d h e r e . F o r what has b e e n c a l l e d n o n - s t o c h a s t i c e f f e c t s ( 1 0 ) - p e r h a p s a s omewhat a r t i f i c i a l n o t i o n - t h e l i m i t S y s t e m h a s b e e n r e t a i n e d . F o r t h e s t o c h a s t i c e f f e c t s , i . e . h e r e d i t a r y e f f e c t s a n d r a d i a t i o n c a r c i n o g e n e s i s , w h i c h a r e of p r e d o m i n a n t c o n c e r n i n r a d i a t i o n p r o t e c t i o n , I C R P h a s s h i f t e d t o w a r d s an a s s e s s m e n t S y s t e m t h a t a i m s a t an o p t i m i z a t i o n of d e t r i m e n t and b e n e f i t . To be p r a c t i c a b l e s u c h a S y s t e m r e q u i r e s t h e a s s u m p t i o n o f l i n e a r i t y o f t h e d o s e - e f f e c t r e l a t i o n a t s m a l l d o s e s , a p o s t u l a t e t h a t i s , a t l e a s t f o r r a d i a t i o n c a r c i n o g e n e s i s , e n t i r e l y h y p o -t h e t i c a l .

The a s s e s s m e n t s y s t e m ha d e f i n e a n d i n t r o d u c e i n t o p r o t e c t i o n a new q u a n t i t y e q u i v a l e n t . The new q u a n t i t y ,

s a l s o made i t n e c e s s a r y t o t h e p r a c t i s e o f r a d i a t i o n

t o r e p l a c e t h e f o r m e r d o s e e f f e c t i v e d o s e e q u i v a l e n t , i s

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a d o s e e q u i v a l e n t a v e r a g e d w i t h s p e c i f i e d w e i g h t f a c t o r s o v e r a l l o r g a n s of c o n c e r n . The r u l e s of r a d i a t i o n p r o t e c t i o n f o r i n d i v i d u a l s r e t a i n n u m e r i c a l l y t h e e a r l i e r a n n u a l l i m i t s . One may n o t e t h a t - e x c e p t f o r u n i f o r m e x p o s u r e s of t h e body - t h e l i m i t a t i o n i n t e r m s of t h e new q u a n t i t y i s l e s s r e s t r i c t i v e t h a n t h e e a r l i e r l i m i t a t i o n i n t e r m s of t h e maximum d o s e e q u i v a l e n t i n an o r g a n . I n f a c t , i t h a s b e e n n e c e s s a r y t o i n t r o d u c e a d d i t i o n a l l i m i t a t i o n s on c e r t a i n o r g a n d o s e s t o e n s u r e t h a t n o n - s t o c h a s t i c e f f e c t s be a v o i d e d .

The new System and i t s i m p l i e d a s s u m p t i o n of l i n e a r i t y have a l s o b e e n r e s p o n s i b l e f o r t h e i n c r e a s e d u s e of c o n c e p t s s u c h as c o l l e c t i v e d o s e ( e q u i v a l e n t ) o r c o m m i t t e d c o l l e c t i v e d o s e ( e q u i v a l e n t ) . I t i s n o t s u r p r i s i n g t h a t t h e s e new, and somewhat c o n t r i v e d , n o t i o n s l e a d t o n o v e l c o n c e p t u a l d i f f i c u l t i e s when a p p l i e d t o s p e c i f i c s i t u a -t i o n s . T h e r e have a l s o b e e n new p r o b l e m s i n r a d i a t i o n - p r o -t e c t i o n m o n i t o r i n g . I t had b e e n t h e p r a c t i s e t o e m p l o y f o r p u r p o s e s of a r e a m o n i t o r i n g , or f o r p e r s o n a l m o n i t o r i n g , q u a n t i t i e s t h a t p r o v i d e c o n s e r v a t i v e r a t h e r t h a n b e s t e s t i m a t e s . W i t h i n t h e new p h i l o s o p h y t h i s i s i n a d e q u a t e . A c c o r d i n g l y t h e ICRU i s a b o u t t o p r e s e n t t h e d e f i n i t i o n of o p e r a t i o n a l q u a n t i t i e s f o r r a d i a t i o n p r o t e c t i o n t h a t c a n be d e t e r m i n e d i n a r e a m o n i t o r i n g a n d p e r s o n a l m o n i t o r i n g . T h e s e q u a n t i t i e s , a m b i e n t d o s e e q u i v a l e n t and i n d i v i d u a l d o s e e q u i v a l e n t , w i l l s e r v e as f a i r , i f s t i l l s omewhat c o n s e r v a t i v e e s t i m a t e s of e f f e c t i v e d o s e e q u i v a l e n t . When t h e s e q u a n t i t i e s a r e i n t r o d u c e d i n t o t h e p r a c t i s e of r a d i a t i o n p r o t e c t i o n a r e a s o n a b l e c o m p r o m i s e b e t w e e n t h e l i m i t and t h e a s s e s s m e n t S y s t e m m i g h t be a c h i e v e d . H o w e v e r , i t must be n o t e d t h a t any e p i d e m i o l o g i c a l i n v e s t i g a t i o n w i l l r e q u i r e i n f o r m a t i on b e y o n d t he summary d o s e s d e t e r m i n e d f o r r a d i a t i o n p r o t e c t i o n mon i t o r i n g . Th e r u l e s o f r a d i a t i o n p r o t e c t i on a r e a i m e d a t l< e e p i n g t he r i sk s u f f i c i e n t l y l o w t o be u n o b s e r v a b l e s t a t i s t i c a l l y . I f e x p o s u r e s bey on d s u c h s a f e 1e v e 1 s o c c u r , do s i m e t r i c I n f o r m a t i o n i s n e e d e d be y o n d r o u t i n e r e q u i r erne n t s . E f f e c t i v e d o s e e q u i v a l e n t , or i t s o p e r a t i o n a l s u b s t i t u t e s , c a n n o t be su i t ab 1e r e f e r e n ce p a r a m e t e r s f o r r a d i a t i o n e p i d e m i o l o g y .

M i c r o d o s i m e t r y

The c h a n g e f r o m do s e e q u i v a l e n t t o e f f e c t i v e do s e e q u i v a l e n t i s t 0 ac c ou n t f o r t h e m a c r o s c o p i c d i s t r i bu t i on

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o f a b s o r b e d d o s e . A n o t h e r c u r r e n t d e v e l o p m e n t i n r a d i a t i o n p r o t e c t i o n r e l a t e s t o t h e m i c r o s c o p i c d i s t r i b u t i o n of r a d i a t i o n e n e r g y . T h i s i s t h e p o s s i b l e r e v i s i o n of t h e q u a l i t y f a c t o r s .

M i c r o d o s i m e t r i c c o n s i d e r a t i o n s ( 2 3 ) h a d f i r s t l e d t o t h e r e c o g n i t i o n t h a t t h e l i n e a r c o m p o n e n t of t h e d o s e -e f f e c t r e l a t i o n i s r e l a t e d t o t h e a v e r a g e e n e r g y c o n c e n t r a t i o n p r o d u c e d i n s u b c e l l u l a r r e g i o n s by S i n g l e e v e n t s , w h i l e t h e q u a d r a t i c c o m p o n e n t r e f l e c t s a c u m u l a t i v e damage due t o t h e i n t e r p l a y o f s e v e r a l e v e n t s . T h e r e i s no c e r t a i n t y , as y e t , on t h e c r i t i c a l d i s t a n c e s f o r w h i c h t h e e n e r g y c o n c e n t r a t i o n s a r e r e l e v a n t . H o w e v e r - l a r g e l y i n d e p e n d e n t of t h e d i s t a n c e s - one has a r a t i o of a v e r a g e S i n g l e e v e n t s i z e s f o r f a s t n e u t r o n s and f o r s p a r s e l y i o n i z i n g r a d i a t i o n s of 30 t o 6 0 . A t l o w d o s e s w h e r e t h e l i n e a r c o m p o n e n t of t h e r a d i a t i o n a c t i o n p r e d o m i n a t e s one e x p e c t s , t h e r e f o r e , RBE v a l u e s of n e u t r o n s v e r s u s s p a r s e l y i o n i z i n g r a d i a t i o n s of t h i s m a g n i t u d e . F o r n e u t r o n s of a b o u t 40 0keV t h e RBE was i n d e e d f o u n d , i n v a r i o u s e x p e r i m e n t s , t o r e a c h s u c h v a l u e s or s t i l l l a r g e r o n e s ( 2 3 ) . P e r h a p s e v e n more i m p o r t a n t l y , an i n v e r s e d e p e n d e n c e of t h e n e u t r o n RBE on t h e s q u a r e r o o t o f t h e n e u t r o n d o s e h a s b e e n c o n s i s t e n t l y f o u n d i n t h e s e e x p e r i m e n t s , w h i c h c o r r e s p o n d s t o a 1 i n e a r - q u a d r a t i c d o s e d e p e n d e n c e o f t h e u n d e r l y i n g damage f o r b o t h r a d i a t i o n s . T h i s has b e e n s o , e v e n when t h e d o s e - e f f e c t r e l a t i o n s w e r e s u b s t a n t i a l l y d i f f e r e n t f r o m t h e 1 i n e a r - q u a d r a t i c r e l a t i o n . One c o n c l u d e s t h a t t h e R B E - d o s e d e p e n d e n c e i s more f u n d a m e n t a l and more c l o s e l y i n d i c a t i v e of t h e i n i t i a l s t e p s of r a d i a t i o n a c t i o n t h a n t h e d o s e - e f f e c t r e l a t i o n w h i c h may be c o - d e t e r m i n e d by c o m p l e x t i s s u e f a c t o r s .

On t h e b a s i s of t h e T6 5 Oak R i d g e d o s i m e t r y i t a p p e a r e d t h a t t h e d o s e - e f f e c t r e l a t i o n f o r l e u k e m i a i n H i r o s h i m a c o m p a r e d t o t h e one f o r N a g a s k i was i n a g r e e m e n t w i t h t h e h i g h n e u t r o n RBE ( 2 4 , 2 5 ) . The r e s u l t a n t h i g h r i s k v a l u e s f o r n e u t r o n s may h a v e b e e n an a d d e d m o t i v a t i o n f o r t h e r e v i s i o n of t h e T65 d o s i m e t r y . As of now, t h e e s t i m a t e s of t h e n e u t r o n d o s e s a r e so s m a l l , e v e n f o r H i r o s h i m a , t h a t no c o n c l u s i o n s on n e u t r o n RBEs c a n be e x p e c t e d f r o m t h e J a p a n e s e d a t a . T h i s g i v e s a d d e d i m p o r t a n c e t o e x p e r i m e n t a l d a t a and t o new e v i d e n c e on h i g h n e u t r o n RBE, s u c h a s t h e l i f e s h o r t e n i n g d a t a f r o m t h e A r g o n n e e x p e r i m e n t s ( 2 6 ) a n d t h e t r a n s f o r m a t i o n d a t a o b t a i n e d by Han e t a l . ( 2 7 ) w i t h f r a c t i o n e d n e u t r o n e x p o s u r e s .

I n v i e w of t h e s e d e v e l o p m e n t s c e r t a i n c h a n g e s a r e e n v i s a g e d . I f , as i t a p p e a r s now, t h e RBE o f d e n s e l y i o n i z i n g r a d i a t i o n s c o n t i n u e s t o r i s e a t s m a l l d o s e s b e l o w

138

a few mGy, h i g h e r q u a l i t y f a c t o r s w i l l h a v e t o be a d o p t e d f o r s t o c h a s t i c e f f e c t s . The c h a n g e w i l l be u n a v o i d a b l e , b e c a u s e i t i s a b a s i c t e n e t of t h e a s s e s s m e n t System t h a t r i s k e s t i m a t e s be r e a l i s t i c a n d t h a t o p t i m i z a t i o n be a p p l i c a b l e e v e n t o d o s e s s u b s t a n t i a l l y b e l o w a n n u a l l i m i t s . A s u b s t a n t i a l c h a n g e o f t h e q u a l i t y f a c t o r s w i l l , on t h e o t h e r b a n d , make t h e new v a l u e s i n a p p l i c a b l e t o n o n -s t o c h a s t i c e f f e c t s . F o r t h e s e e f f e c t s t h e l i m i t i n g p r i n c i p l e i s s t i l l r e t a i n e d , w i t h d o s e - e q u i v a 1 e n t l i m i t s i n e x c e s s o f 0.1 s i e v e r t . I t i s d i f f i c u l t t o i g n o r e t h e d u a l i s t i c n a t u r e of t h e p r e s e n l System of r a d i a t i o n p r o t e c t i o n .

A c k n o w l e d g e m e n t T h i s work has b e e n p a r t l y s u p p o r t e d by EURATOM

r e s e a r c h c o n t r a c t BIO 2 8 6 D.

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24. H. H. R o s s i and A. M. K e l l e r e r , The V a l i d i t y of R i s k E s t i m a t e s of Leukemia I n c i d e n c e Based on Japanese D a t a , R a d i a t . R e s . 58:131 (1974).

25. H. H. R o s s i and C. W. Mays, Leukemia r i s k from ne u t r o n s , H e a l t h Phys. 34:353 (1978).

26. J . F. Thomson, L.S. Lombard, D. Grahn, F. S. W i l l i a m s o n , and T. E. F r i t z , RBE of F i s s i o n Neutrons f o r L i f e S h o r t e n i n g and T u m o r i g e n e s i s , i n : P r o c ."European Seminar on Neutron C a r c i n o g e n e s i s " , J . J . B r o e r s e and G. B. G e r b e r , eds., 75-93, EUR 8084 EN, Luxembourg, 1982.

27. A. Han and M. M. E l k i n d , T r a n s f o r m a t i o n of Mouse C3H/10T1/2 C e l l s by S i n g l e and F r a c t i o n a t e d Doses of X-Rays and F i s s i o n - S p e c t r u m Neutrons, Cancer Res. 39:123 (1979).

140

INDEX

Abe r d e e n , 65 a b s o l u t e r i s k model, 55 a d d i t i v e i n t e r a c t i o n , 62 a b s o r b e d f a t a l dose, 520 A d u l t H e a l t h S t u d y , 416 a f l a t o x i n , 190 age a t e x p o s u r e , 81, 118 a g e i n g , e f f e c t o f r a d i a t i o n , AIDS, 249 a i r borne p a r t i c l e s , 405 a i r dose c u r v e s , 423 a l k i l a t i n g a g e n t s , 377 a l i p h a t i c h y d r o c a r b o n s , 295 a m b i e n t , 291 ambient dose e q u i v a l e n t , 137 A m e r i c a n Embassy p e r s o n e l i n

Moscow, 487 a n a l y t i c a l e p i d e r m i o l o g y , 499

a t a x i a t e l a n g i e c t a s i a , 205, 236, 246

Autopsy Pathology Program, 415 a v i a t i o n (commercial), 371 8-azaguamine, 188 azathioprine, 510

69 background r a d i a t i o n , 40, 65 bactenophage T4, 239 BALB-MSV, 226 BEIR committee, 52, 64, 110, BHK-21 c e l l s , 162 B-K mole Syndrome, 216 B-lym, 227 benign breast disease, 481 benzene, 48, 30 benzo-(a)pyrene, 159, 161, 199,

239

426

anchorage independence, 158, 165 b e n z o y l t r i c h l o r i d e , 316 and DNA repair, 195

a n k y l o s i n g Spondylitis, 71, 141, 142, 149, 273

a n i r i d i a , 390 a n n u a l l i m i t o f i n t a k e ( A L I ) , a r a , C, 247 a r s e n i c , 8, 301, 400 a r s e n i c Compound, 18 a r s e n i c t r i o x i d e , 320 a r t i f i c i a l menopause, 144 a s b e s t o s , 176, 182, 309, 314 a s b e s t o s i s , 308 a t o m i c bomb s u r v i v o r s , 9, 73,

b e t a - n a p h t h y l a m i n e , 511 106, B i o l o g i c a l E x p o s ure i n d i c e s , 292

B i o l o g i c a l M o n i t o r i n g programs, 291, 296

, 3 9 0 B i o l o g i c a l Q u a l i t y G u i d e , 296 b i o r e d u c t i v e enzime d e f i c i e n c y ,

260 b i s c h l o r o m e t h y l e t h e r , 18 b l a c k l u n g d i s e a s e , 307 b l a d d e r c a n c e r / c a r c i n o m a , 168,

230, 313, 316, 320, 511 b l e o m y c i n , 513

82,bone c a n c e r , 55, 111 107, 127, 146, 283, 390, bone c e l l s , 9 414, 515, 518 bone marrow c a n c e r ,

A t o m i c bomb C a s u a l i t y Commission b r a i n c a n c e r , 320 383, 414, 516

566

573

breast cancer age incidence curves, 480 and leukemia, 506 cancer gene f 490 estrogen receptor, 481 e t i o l o g y , 479 exposure-age, 82 f a m i l i a l Syndrome, 255 genetic f a c t o r s , 480 i n i t i a t i o n and promotion, 489 i n AHS, 416 incidence, 51 post/pre menopausal, 481 r a d i a t i o n , 313, 566 r i s k f a c t o r s , 482 t u b e r c o l o s i s p a t i e n t s , 7

b r o n c h i t i s , 405

cadmium, 20, 293 cancer/Carcinoma

bladder, 230, 313, 511 b r a i n , 322 breast, 7, 51, 82, 255, 313,

416, 506, 479 cervix, 150 choroidal melanoma, 323 colon, 59, 230 c o l o r e c t a l , 507 d i g e s t i v e system, 444 epidermoid, 401 e p i t e l i a l , 112, 119 esophageal, 316 eye melanoma, 323, 476 g a s t r o i n t e s t i n a l , 507 glioblastoma, 258 hematopoietic, 227 Hodgkin's, 249, 324, 503 Hutchinson 1s malignant

f r e c k l e , 474 kaposi sarcoma, 249 l e n t i g o maligna, 474 leukemia (see leukemia) l i v e r , 7 l i v e r angiosarcoma, 294, 315 lung (see lung Carcinoma) mammary, 230 melanoma, 9, 253, 322, 474 mesothelioma, 176, 308 multiple myeloma, 505

multiple p o l i p o s i s , 259 nasal cancer, 313, 322 nevoid basal, 215 neuroblastoma, 230 osteosarcoma, 273 ovarian, 506 retinoblastoma, 215, 390 skin cancer, 12, 565 stomach, 9, 59, 322 t e s t i c u l a r , 322, 509 t h y r o i d , 12, 51, 416, 561 v a g i n a l , 315 Wilms', 390

cancer r i s k assessment, 2 baseline incidence, 50 c e r v i x cancer treatment, 79 compensation, 49, 61 dose-rate e f f e c t s , 97 genetic r i s k , 394 f a m i l i a l d isorders, 235 models/modelling, 96, 100 natural r a d i a t i o n , 10 occupational exposures, 8 occupationally r e l a t e d , 49 prone-families, 213, 254 prone races, 52 r a d i a t i o n induced, 74 radiotherapy, 5 s p o n d i l i t i s p a t i e n t s , 86

cancer proneness (see s u s c e p t i b i l i t y )

cancer prone f a m i l i e s , 213 cancer s u s c e p t i b i l i t y

DNA r e p a i r , 206 genetic, 235 i n d i v i d u a l , 20 population, 105

cancer t o t a l incidence, 323 carbon d i s u l f i d e , 308, 311 carbon monoxide, 21

b i o l o g i c a l monitoring, 40 cardiovascular disease, 40

carcinogens e a r l y and l a t e a c t i n g , 181 hyperresistance, 254

cardiovascular diseases, 416 cardiovascular m o r t a l i t y , 40 cardiovascular t o x i c i t y , 311

574

c a t a r a c t s , 447 CBA mice, 95 CB r a d i o s , 434 c e l l k i l l i n g e f f e c t , 68, 79, 85,

94, 101, 109, 111, 118, 153

c e l l transformation (see transformation)

c e l l u l a r c h e m i o s e n s i t i v i t y , 249 censoring of data, 270 c e r v i x cancer, 150 chemical hazards, 537 c h l o r i n a t e d benzenes, 26 c h l o r i n a t e d phenols, 26 chloracne, 540 chlornaphazine, 511 chloro-methyl-ether, 316 Cholinesterase, 293 chondrodystrophy, 396 c h o r o i d a l melanoma, 323 chromium, 18, 302 chromosome aberration/abnorm-

a l i t i e s , 283, 384, 391, 429 chromosome breakage disorders,

214 chronic lymphatic leukemia, 4 c h r y s o t i l e miners, 176 c h r y s o t i l e t e x t i l e workers, 176 C 3H/10Ti c e l l s , 162 c i t o t o x i c i t y of base damage,

376 c l i n i c a l studies versus

epide m i o l o g i c a l , 19 c o a l power pl a n t s , 371 c o a l workers, 307 c o l l e c t i v e dose, 137 c o l l i s i o n s t o p p i n g power, 342 colon C a r c i n o m a , 59, 230 combined parental expostire, 386 comparability, 40 comparison group choice, 40, 144 compensation, 52, 60 competing r i s k , 270, 286 confounding e f f e c t s / f a c t o r s , 36,

39, 150, 530 congenital abnormalities, 365,

544 Connecticut Tumor Registry, 508 consumer products, 370

continuous c e l l l i n e s , 162 c o s t - b e n e f i t a n a l y s i s , 348 Cox algoritm, 276, 289 c r o c i d o l i t e , 176 C-retroviruses, 459 c r o s s - l i n k s , 260 cumulative tumor incidence, 272 cumulative tumor r a t e , 271 curable Cancers, 569 cyclamates, 318 cyclophosphamide, 504

death/absolute and r e l a t i v e r i s k , 54, 78

delayed gammas, 422 delayed r a d i a t i o n , 127 N-7 deoxyguanosine, 375 detection l i m i t s , 299 determinants of diseases, 33, 37 N6-d guo, 377 (eis)-diaminedichloroplatium,

257 d i e s e l truck d r i v e r s , 316 d i e t h y l s t i l b e s t r o l , 315, 161 dieneephalic Syndrome, 444 d i g e s t i v e System cancer, 322 dimethylmitrosamine, 375, 377 d i o x i n s , 537 d i r e c t standardisation, 42 D i s p l a s t i c Nevus Syndrome, 215,

253 sporadic v a r i a n t , 220

DNA apu r i n i c s i t e , 240 base damage c i t o t o x i c , 376 blocking damage, 195 damage accumulation, 378 damage mutagenic and cancerogenic, 375

damage r e p a i r , 187 f a u l t y metabolism, 235 g l i c o s y l a s e , 240 l e s i o n s from carcinogens, 191,

236 l i g a s e , 245 methyltransferase, 198 polimorphism, 395 recombinant methods, 430 r e p a i r and skin cancer, 205 sequencing, 395

575

synthesis an damaged template 236

transmethylase, 249 unrepaired l e s i o n s , 187, 197,

242 UV endonuclease S i t e s , 243

DNA r e p a i r (see repair) DNA tumor v i r u s e s , 168 dose

assessment, 369 d i s t r i b u t i o n , 358 equivalent, 342 equivalent f or i n f a n t s , 368 estimate f o r AT survivors, 415 l i m i t s , 349 l i m i t a t i o n ICRP system, 346,

364, 369 monitoring, 369 optimization, 347, 364 rate e f f e c t s , 97 rate e f f e c t i v e n e s s f a c t o r

(DREF), 97 response, 42, 65, 77 to organs (see organ dose)

dosymetry T65 (see T65) Down's Syndrome, 390, 459 drugs carcinogenic p o t e n t i a l ,

499 drosophila, 15 double Strand break, 376

ecogenetic, 236 E . c o l i , 239 e f f e c t i v e dose equivalent, 4,

136, 343, 365 EJ human bladder Carcinoma, 168 E l a gene, 169 e l e c t r o p h o r e t i c v a r i a n t s , 392 endometrial Carcinoma, 317 env oncogene, 460 environmental monitoring, 291 enzyme d e f i c i e n c y , 392 epidemiological studies, 19 epidermoid cancer, 401 e p i t e l i a l Cancers, 112 e p i l o i a , 390 erb-B oncogene, 466 esophageal cancer, 316 estrogen, 317

e t h y l a t i n g agents, 375 ethylate dihromide, 312 e t h y l n i t r o s u r e a , 157, 378 e t i o l o g i c f r a c t i o n , 38 e x c i s i o n r e p a i r , 188

anchorage independence, 197 c e l l c ycle dependence, 193 d e f i c i e n t XP c e l l s , 193 i n Gl c e l l s , 193 r a t e , 190

exposure age at, 270 a s c e r t a i n i n g , 147 assessment, 19, 293, 296 b i o l o g i c a l i n d i c e s , 292 combined parental, 386, 389 dioxins, 542 duration, 185 Edinburgh, 65 environmental, 24 e p i t e l i a l Cancers, 112, 114,

119 indoor, 24 l i f e t i m e r i s k , 120 l i m i t s , 302 medical, 363, 368, 3 71 non occupational, 363 occupational, 24, 339, 359 paraoccupational, 24 q u a n t i t a t i v e , 24 to microwave, 433 to the p u b l i c , 371

extrapolation, 152, 378 eye c o l o r , 476 eye melonoma, 323, 476

f a l l o u t , 370 f a m i l i a l cutaneus malignant

melanoma, 214 f a t a l accident rates i n

industry, 553 f a t a l i t y annual rate occupa­

t i o n a l , 308 Fat Man, 420 Federal Tort Claim Act, 49 F l M o r t a l i t y Study, 365, 388 focus formation, 158 follow-up of cohorts, 499

of p a t i e n t s , 500

576

f r a c t i o n a l uptake, 19 f r a c t i o n a t i o n of dose, 81 Fuchsin dye, 315

gametic doubling dose, 389 Gardner Syndrome, 249 genetic and cancer r i s k s , 394 genetic e f f e c t s , 430, 567

biochemical l e v e l s , 417 genetic l e s i o n s i n human

tumors, 229 genodermatoses, 214 glioblastoma, 258 G0 r e l e a s e , 190 growth f a c t o r s , 462 guanil adducts, 246

h a i r , 471 Ha-ras oncogene, 168 hamartomatous disorders, 214 Harm ( i n d u s t r i a l ) , 557 Harvey murine sarcoma v i r u s , 225 health,

hazards q u a n t i f i c a t i o n , 42 physics research reactor, 424 r i s k assessment, 17, 26, 293 s u r v e i l l a n c e , 292, 321

healthy worker e f f e c t , 34, 40 hermatopoietic neoplasms, 122 hemoglobin a l k i l a t i o n , 377 hereditary Cancers, 215 heterozygotes frequency, 529 hexachlorocyclohexane, 26 h i g h - f a t d i e t , 488 h i t and target theories, 130 HLA phenotypes, 392 Hodgkin's disease, 346, 503 hormones synergism with

r a d i a t i o n s , 282 HPRT, 188 HS, 250, 228, 241 HSO, 230 human epidermal growth factor

receptor, 466 human f i b r o b l a s t , 165 human oocyte, 387 human p l a t e l e t derived growth

f a c t o r , 462 HUT 14 c e l l s , 165 Hutchinson'd maglignant f r e c k l e ,

473

hypermutable f i b r o b l a s t i n DNS, 221

hypothesis V a l i d a t i o n , 317

IARC animal carcinogens, 312, 511

ICRP, 340, 346 immune d e f i c i e n c y states, 214 increased r a d i o r e s i s t a n c e , 256 i n d e f i n i t e l i f e s p a n ( c e l l u l a r ) ,

166, 160 i n d i v i d u a l dose equivalent, 137 Infant Autopsy Program, 181 i n h a l a t i o n studies, 284 in-houses radon, 368, 370 i n i t i a t i o n and promotion, 181 inorganic lead, 296, 302 i n s u l a t i o n workers, 177 i n t e l l i g e n c e t e s t s , 521 i n t e r a c t i o n models, 56 i n t e r n a l emitters, 128 in-utero exposure, 66, 568

age at, 81 carcinogenic e f f e c t , 143, 148 childhood cancer, 146 nervous System, 515 r a d i a t i o n r i s k , 81 twin, 67

ischemic heart disease, 322 i s o t o n i c regression, 282

j u s t i f i c a t i o n , 347, 364

Kaplan-Meier formual, 273, 282 Kaposi sarcoma, 249 Kerala, 11 keratoses, 476 kerma, 125, 341, 414, 422 Kirsten leukemia v i r u s e s , 225 K i r s t e n murine sarcoma v i r u s ,

225 K l i n e f e l t e r ' s Syndromes, 390 Korean war veterans, 437

large bowel cancer, 322 lead, 20, 298 l e n t i g o maligna, 474 l e t h a l l e s i o n s and c r i t i c a l c e l l

p r o t e i n s , 195

577

leukemia, 14, 65 actinomyGin D, 509 acute myeloid, 38 adiuvant chemotherapy, 500 adriamicin, 510 age at exposure, 83, 84, 106 a l k i l a t i n g agents, 505 and a p l a s t i c anemia, 72 and tho r o t r a s t , 7 ankylosis s p o n d i l i t u s , 80, 106

111 antimetabolite therapy, 509 atomic bomb survivors, 107 benzene and x i l e n e , 313 bone marrow dose, 60 breast Carcinoma, 508 busulphan, 509 chemotherapy r e l a t e d , 499 c h i l d r e n of AT survivors, 390 chlorambucil, 506 chronic g r a n u l a c t i c , 58 c o l l o i d a l gold, 502 c o l o r e c t a l cancer, 507 cumulative bone marrow dose,

504 cumulative r a t e , 271 cyclophosphamide, 504 cytoxan, 509 duration of chemotherapy, 504 excess deaths, 427 g a s t r o i n t e s t i n a l cancer, 507 high-low r a t e , 51 hydroxyurea, 510 i n CBA mice, 79 i n Hodgkin's disease, 503 latency period, 106 l i f e t i m e r i s k , 113, 351 lung Carcinoma, 509 lymphocytic, 313 melphalan, 506 methotrexate, 510 MOPP, 502 multiple myeloma, 505 myelogenous, 500 myeloid i n mouse, 94 natural r a t e , 151 non-lymphocytic, 500 ovarian cancer, 506

Pierce-model, 111 platinum, 510 policythemia vera, 506 p r o b a b i l i t y of causation, 59 r a d i a t i o n induced, 75, 313 r e g i s t r y , 406 r i s k i n time, 74, 425 rubber workers, 322 s t r e p t o z o t o c i n , 508 temporal pattern of r i s k , 106 t e s t i c u l a r cancer, 509 t r e o s u l f a n , 507 v i n c r i s t i n e , 510 VP 16, 510

l i f e long r i s k , 178 l i f e shortening e f f e c t , 68 l i f e span study, 415, 420 l i f e time r i s k , 110 Li-Fraumeni f a m i l i a l Syndrome,

255 l i n e a r dose response model, 52 l i n e a r quadratic,

r i s k estimates, 52 dose-response function, 100 dose-effects, 109

L i t t l e Boy, 420 Livemore, 315 l i v e r angiosarcoma, 294, 315 l i v e r cancer, 7 l o c a t i o n of AB survivors, 414 long term problems, 367 Love Canal, 21, 48 low doses r i s k , 12 lung cancer

arsenic, 313 asbestos workers, 179 by shipyards, 313 f i s s i o n neutron, 284 fluospar miners, 400 goldminers, 400 hematite miners, 400 high and low r a t e , 51 h i s t o l o g y , 400 i n butchers, 313 indoor radon, 4 1 , 402 i n s u l a t i o n workers, 177 K-ras oncogene, 226 Livemore, 325

578

Lung c a n c e r ( c o n t i n u e d ) maximum o f r i s k , 401 mo d e l , 178 motor v e h i c l e s d r i v e r s , 321 m u s t a r d g a s , 315 N a v a j o I n d i a n s , 404 n i c k e l w o r k e r s , 180 p a i n t e r s , 322 p r o b a b i l i t y o f c a u s a t i o n , 59 r a d i a t i o n , 566 r i s k , 8, 176 s m a l l c e l l , 401 s m e l t e r s , 313 sm o k i n g , 57, 177 s u g a r cane f a r m e r s , 322 t i n m i n e r s , 322 u r a n i u m m i n e r s , 8, 87, 399,

556

m a l i g n a n c i e s n a t u r a l r a d i a t i o n i n d u c e d , 4

mammary c a r c i n o g e n e s i s , 487 mammary Carcinoma, 230 mammary g l a n d d i f f e r e n t i a t i o n ,

487 mammary tumor r a t e , 278 marrow d o s e , 79, 81 m a t c h i n g i n c o h o r t s t u d i e s , 41 m a t e r n a l m a l n u t r i t i o n , 529 melanoma, 4, 253, 322, 324, 474 melanoma p r o n e f a m i l i e s , 215 menopause r a d i a t i o n i n d u c e d ,

70, 144 m e n t a l h e a l t h , 21 m e n t a l r e t a r d a t i o n i n AB

s u r v i v o r s , 515, 518 Mer, 376 Mer p h e n o t y p e , 247 me r c u r y , 21 m e s o t h e l i o m a , 176, 179, 308 m e t a b o l i c a c t i v i a t i o n , 377 m e t a l s

a b s o r b e d , 292 s p e c i a t i o n , 301

0 6 - m e t h y l g u a n i n e , 247, 375 methylene Chloride, 40 8-methoxypsoralen, 260 m e t h y l m e t h a n e s u l f o n a t e , 377 micrococcus l u t e u s , 239, 256

m i c r o d o s i m e t r y , 124, 129 r a d i o p r o t e c t i o n , 138 s p e c i f i c e n e r g y , 133

microwave r a d i a t i o n as c o - c a r c i n o g e n , 451 e x p o s u r e d o s e , 436 m a l i g n a n t n e o p l a s m s , 437 m o r b i d i t y s t u d i e s , 442 m o r t a l i t y s t u d i e s , 435 r e p r o d u c t i v e e f f i c i e n c y , 450

m i t o m y c i n C, 258 MMC h y p e r r e s i s t a n c e and c a n c e r

p r e d i s p o s i t i o n , 258 MNNG, 198 MNNG t r e a t e d a d e n o v i r u s e s , 248 models

age l i n e a r , 115 c a r c i n o g e n e s i s , 175 e r r o r , 184 i n c i d e n c e r a t e o f t u m o r s , 113 l u n g c a n c e r , 178 m e s o t h e l i o m a , 179 m u l t i - s t a g e , 181 P i e r c e , 111 p r o p o r t i o n a l h a z a r d s , 275 r e l a t i v e r i s k , 109 t i m e i n c o r p o r a t e d , 101 t i m e l i n e a r , 115 t i m e s h i f t , 279 tumor i n c i d e n c e and do s e , 100 tw o - s t a g e m u t a t i o n a l , 101 W e i b u l l , 280

Moloney l e u k e m i a v i r u s , 225, 460 Monazide s a n d s , 11 m o n i t o r i n g , 291 Mormons, 51 m o r p h o l o g i c a l t r a n s f o r m a t i o n , 161 m o r t a l i t y

f r o m c a u s e s o t h e r t h a n c a n c e r , 425

r a t e i n i n f a n t and c h i l d h o o d , 385

mouse o o c y t e , 387 mouse r a d i a t i o n s t u d i e s , 94 m u l t i p l e e x p o s u r e , 36 m u l t i p l e p o l i p o s i s / s a r c o m a

f a m i l y , 259 m u l t i p l i c a t i v e i n t e r a c t i o n , 56,

82

579

mutation induction, 188 myc oncogene, 169, 467 myelodisplastic Syndromes, 501

N-acetoxy-2-acetylaminofluorene, 239

nasal cancer, 313, 322 natural r a d i a t i o n , 10, 339, 363,

368 neoplastic transformation, 163 nervous system microwave

e f f e c t s , 445 Nevada t e s t , 419 Nevi natural h i s t o r y , 216 nevoid basal c e l l Carcinoma

Syndrome, 215 neurastenic Syndrome, 444 neurablastoma, 230 neurofibromatosis, 390 neuronal migration, 529 neutron

exposure, 385 kerma, 422 RBE, 167 r e s i d u a l r a d i a t i o n , 413

NIH/3T3 c e l l s , 460 n i c k e l , 18, 302 n i c k e l r e f i n e r y workers, 180 nine parameters formula, 424 nigrogen mustard, 503 4 - N i t r o q u i n o l i n d-oxide, 221,

239, 246, 260 N-methy1-N1-nitro-N-nitrosoguani

dine, 246 N-methyl-N-nitrosourea, 247

age increasing t o x i c i t y , 251 non-stocastic processes, 206 N-ras oncogene, 226 nuclear reactors releases, 370

Occupational i n j u r i e s , 552 s u r v e i l l a n c e , 334 t o x i c i t y , 310

ocular e f f e c t s of microwave, 447 odds r a t i o , 39 oncogenes, 168 onc-proteins, 462

optimization of dose, 347 organ dose, 53, 58, 127, 136,

344, 350, 366, 374, 420

organochlorine contaminants, 302 ORNL studies, 97 osteosarcoma, 273, 280 over-exposed workers management,

354 ovarian cancer, 506 ovaries x - i r r a d i a t e d , 70

Pace-Marcum dosymetry, 425 p a r t i c u l a t e - x - e m i t t e r s , 128 p21 coding sequences, 228 personal dosimetry, 47 phosphoglucomutase, 393 photoreactivation, 206, 241 Pierce model, 111 pneumoconiosis, 307 point mutation, 229 polycythemia vera, 511 polyoma v i r u s , 159, 169

middle T gene, 169 large T gene, 169

power density of microwave, 434 pregnancy

l o s s , 20 outward r a t e , 387

premature death, 384 p r o b a b i l i t y of causation

t a b l e s , 49 Cancers, 59

procarbazine, 503 prompt r a d i a t i o n , 421 p r o t e i n kinase, 462 p r o t e i n molecules abnormaities,

392 prato oncogenes, 225, 459 p 28 s i s processing, 463 pyrimidine dimers, 190, 206, 237,

376

r a d i a t i o n DNA synthesis depression, 258 hormones synergism, 282 induced menopause, 70 i n t e r a c t i o n s , 82

5 8 0

r a d i a t i o n (continued) occupational exposure, 339 smoking i n t e r a c t i o n , 57 t o t a l population exposure, 64

r a d i a t i o n carcinogenesis animal studie s , 94 epidemiological studies, 3 t i s s u e f a c t o r s , 136

Radiation E f f e c t s Research Foundation, 383, 414, 516

r a d i a c t i v e nuclides r e p o s i t o r i e s , 364

r a d i o l o g i s t s , 68, 145 r a d i o n u c l i d e s , 4 radiofrequency bands, 435 r a d i o r e s i s t a n c e increased i n

Cancer prone f a m i l i e s , 257 radiotherapy

a n k i l o s i n g S p o n d y l i t i s , 71 cervix cancer, 71 non- malignant diseases, 6

radiowave sickness, 444 radium, 224, 128, 273 radium d i a l p a i n t e r s , 9 radon, 8, 551

daughter products, 9, 128, 400 indoor exposure, 4 1 , 368, 370,

402 miners 1 exposure, 41 q u a n t i t a t i v e r i s k , 406

ras oncogene, 169, 225, 472 i n human cells/tumors, 131,

230 r a t brain tumor, 157 r a t mammary tumor, 157 Rous sarcoma v i r u s , 167, 459 RBE, 342, 419 reference l e v e l s , 350 r e f r a c t o r y anemia, 501 r e p a i r (DNA-repair)

aberrant, 242 a l k y l r e p a i r i n sraokers, 211 a l k y l t r a n s f e r , 206 and cancer s u s c e p t i b i l i t y , 207 bulky l e s i o n - r e p a i r complex,

244 c e l l c ycle dependence, 197 daughter Strand, 237

r e p a i r (continued) d e f i c i e n c y and breast cancer,

485 d e f i c i e n t c e l l s , 187 i n AT c e l l s , 246 i n c i s i o n step, 239 i n m i c r o b i a l Systems, 240 i n XP c e l l s , 242 l e v e l s i n t i s s u e s , 378 mgchanisrns, 98, 206 O -methylguanine, 198, 247,

375 4 NQO l e s i o n s , 246 nucleotide e x c i s i o n , 206, 239,

245 rate i n human c e l l s , 380 time a v a i l a b l e , 195 transformation, 187 V a r i a t i o n , 207

r e s p i r a t o r y volume, 25 r e t i n o l binding p r o t e i n , 20 retinablastoma, 215, 389 r e t r o v i r u s e s , 225 Rh locus, 219 r i s k

absolute, 53 acceptance/acceptability, 182,

367 by age, 427 bone marrow i r r a d i a t i o n , 7 c o e f f i c i e n t s , 53 comparison, 352, 551 evaluation and duration, 73 estimation, 393 extropolation, 428 genetic, 383 l i n e a r quadratic, 52 l i v e r i r r a d i a t i o n , 7 of CMM, 218 of death i n sport, 308 perception, 182 q u a n t i f i c a t i o n , 4, 218 r e l a t i v e r i s k model, 55

RNA tumor v i r u s e s , 162 Rossi-counters, 130 Rothmund Thomson Syndrome, 253

581

s a f e t y l e v e l s , 2 s a f e t y o f c h e m i c a l s , 311 s a m p l i n g , 151, 298 s e n s i t i v i t y i n d i v i d u a l o r g a n , 4 s e n t i n e l p h e n o t y p e s , 384, 390 s e q u e n c i a l c l o n i n g a s s a y , 163 Seveso a c c i d e n t , 538 Seveso b i r t h d e f e c t r e g i s t r y ,

540 sex dependent d i f f e r e n c e s i n

k i n e t i c s , 294 s i c k l e c e l l anemia, 530 S i m i a n sarcoma v i r u s , 459 S i n g l e gene d i s o r d e r s , 213 s i s oncogene, 459 s i s t e r c h r o m a t i d exchange, 391 s k e l e t a l d o s e , 275 s k i n c a n c e r , 12, 569 SK-H-SH c e l l s , 230 smoking

a l k y l a c c e p t o r l e v e l s , 211 and a r s e n i c t r i o x i d e , 320 and r a d o n , 403 as b e h a v i o u r a l f a c t o r , 33 by m i n e r s , 8, 87 i n f l u e n c e on l u n g c a n c e r , 400 i n p r o b a b i l i t y o f c a u s a t i o n ,

57 i n s u l a t i o n w o r k e r s , 177 m e s o t h e l i o m a , 177 mucous S t i m u l a t i o n , 409 r a d i a t i o n i n t e r a c t i o n , 57

smoke d e t e c t o r s , 371, 373 s o f t x - r a y s , 356 s o l i d tumors f o l l o w i n g

c hemotherapy, 510 s o m a t i c c e l l m u t a t i o n , 160 s p e c i f i c a b s o r b t i o n r a t e , 435 s r c oncogene, 167 (non) s t o c h a s t i c e f f e c t s , 341,

366 stomach c a n c e r , 9, 59, 322 s t r e p t o m y c e s g r i s e u s , 241 s t r e p t o z o t o c i n , 508 s t u d y / i e s

b a s e , 34 c a s e - c o n t r o l , 142, 500 cause d i r e c t , 22, 296 c o h o r t , 142, 499 d e s i g n c h o i c e , 144

s t u d y / i e s ( c o n t i n u e d ) d i s e a s e o r i e n t e d , 143 ex p o s u r e o r i e n t e d , 142 i n d i v i d u a l d i r e c t , 22 o b s e r v a t i o n a l , 142 S i t u a t i o n d i r e c t , 22, 296

s u s c e p t i b i l i t y (see c a n c e r s u s c e p t i b i l i t y )

SW 1271 c e l l s , 230 SW 480 c e l l s , 230

T4 b a c t e r i o p h a g e , 239 T24 b l a d d e r C a r c i n o m a c e l l s ,

226, 241 T24/EJ b l a d d e r tumor oncogene, 228 TCDD, 26 TCDD t e r a t o g e n i c i t y , 538 T65 (Oak Ri d g e ) d o s i m e t r y , 138,

385, 414, 424, 517 t e s t i c u l a r c a n c e r , 323, 509 t h a l i d o m i d e , 532 6 - t h i o g u a m i n e , 188 t h o r i u m , 7 t h o r o t r a s t , 7, Three M i l e I s l a n d , 47 t h r e s h o l d d o s e , 3, 130, 181 t h y r o i d c a n c e r , 4, 12, 51, 416,

566 t h y r o i d g l a n d , 47 t i m e l o s s i n d u s t r i a l i n j u r i e s ,

556 t i m e p i e c e l u m i n o u s , 372 t i n e a c a p i t i s , 515 t i s s u e d o s e , 343, 523 t o l u e n e , 26 T o r t l a w , 45 t o x i c e f f e c t s r e c o g n i z i n g , 310 t o x i c o k i n e t i c s , 293 t r a c e m e t a l s , 40 t r a i n i n g , 353 t r a n s f o r m a t i o n ( i n v i t r o )

a n chorage i n d e p e n d e n c e , 157, 165, 185

a s s a y , 159, 162 DNA r e p a i r , 187 e f f i c i e n c y , 460 f r e q u e n c y , 160 m o r p h o l o g i c a l , 161 p a r t i a l , 168 p r o t e i n s , 459

582

transformation (continued) SV40 v i r u s e s , 198

transforming v i r u s e s , 167, 459 t r i c h l o r o a c e t i c a c i d , 297 TRIS, 312 t r i t i u m , 127, 372 t u b e r c o l o s i s , 273 tuberous scherosis, 253 tumor r e g i s t r y , 416 tumors regression, 166 Turner's Syndrome, 390 t y l o s i s , 215

UNSCEAR, 52, 64, 68, 71, 151, 373, 554, 567

U n i f i e d Population Studies at RERF, 418

unscheduled DNA synthesis, 208 unusual disease recognition,

314 upper bounds, 366 uranium f u e l c y c l e , 340 uranium miners, 8, 87 ü.S. Foreign Service Study, 440 u.V. r a d i a t i o n

aberrant r e p a i r , 242 c e l l k i l l i n g e f f e c t , 221 c i t o t o x i c e f f e c t , 189, 194,

97 endonuclease s e n s i t i v e s i t e s ,

243 e x c i s i o n r e p a i r , 188 f l u x and skin cancer, 205 human f i b r o b l a s t i r r a d i t i o n ,

166 immune system, 379 mutagenic e f f e c t , 189, 194,

202 pyrimidine dimers, 245

vaginal adenocarcinoma, 315 vinca a l k a l o i d s , 513 v i n y l c h l o r i d e metabolites, 294 v i n y l c h l o r i d e monomer, 310 v i t a l Status, 149 v o l a t i l e organic solvents, 292,

300

Waste (radioactive high l e v e l ) , 370

weighting f a c t o r , 344 Weibull model, 280 WHO study lead and cadmium

exposure, 20 Wilms' tumor, 390 workers

a i r c r a f t crew, 339 asbestos, 179, 561 a v i a t i o n e l e c t r o n i c s techni-

cians, 436 Beta naphtalene manufacture,

561 broadcasting t r a n s m i t t e r s , 433 butchers, 313 by shipyards, 313 carpenters, 334 coal miners, 308 c u t t i n g o i l , 561 construction i n d u s t r i e s , 308 d i e s e l truck d r i v e r s , 316, 322 dye f u c s i n preparing, 315 e l e c t r o n i c s technicians, 436 f i r e c o n t r o l technicians, 436 f l i g h t - d e c k crew, 446 f l u o r s p a r miners, 400 goldminers, 400 hangar-deck crew, 446 hematite miners, 400 i n d u s t r i a l radiography, 360,

565 i r o n ore miners, 400 i n s u l a t i o n , 177 miners, 334, 355 motor v e h i c l e d r i v e r s , 321 mustard gas, 315, 561 n i c k l e , 180, 561 nuclear m i l l i n g , 360 nuclear f u e l manufacture, 360 nuclear reactors, 360, 555 nuclear reprocessing, 360, 555 nuclear research, 360, 555 offshore o i l , 308 overexposed, 354 p a i n t e r s , 322 petrochemical, 322

583

workers (continued) p e s t i c i d e a p p l i c a t o r s , 322 phosphate f e r t i l i s e r s , 339 p h y s i o t h e r a p i s t s , 447 pitchblende miners, 561 p r i n t i n g trade, 561 radar Operators, 436, 443 railway s t a f f , 308 rubber, 322, 561 rubber v u l c a n i s i n g , 316 shoe making, 561 smelters, 313 spectacle lens makers, 322

sugar cane farmers, 322 t i n miners, 322 uranium f u e l c y c l e , 340 uranium mining, 399, 556 wood dust, 313, 314

working l e v e l s , 399

Xeroderma pigmentosum, 188, 205, 237, 242, 238

xylene, 26? 313

z i n c Protoporphyrin, 296

584 Bayerische

Staatsbibliothek München