Adv. Space :?e.$. Vol.3,No.8,pp.187—194,1983 0273—1177/83 $0.00 + .50

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UNIQUE BIOLOGICAL ASPECTS OFRADIATION HAZARDS —

AN OVERVIEW

PaulTodd

403 Althouse Laboratory, The Pennsylvania State University,University Park, PA 16802, U.S.A.

ABSTRACT

Low orbit, geostationary, and deep—spaceflights differ from one another with respect to

particle radiation environment, participating population size, mission duration, andbiological risks other than radiation. It is proposed that all of these factors be con-sidered in the setting of safety standards and, in particular, that the rem—dose conceptis applicable only to radiations having low and intermediate linear energy transfer (elec-trons, protons, and helium ions), whereas the incidence of rnicrolesions is a more meaning-ful indicator of the hazard due to higher—Z, high energy (HZE) particles. A microlesion isthe biological injury inflicted in a specific tissue by a single HZE particle, and it is

still in need of quantitative biological definition for specific mammalian tissues.If for example, a microlesion is taken as due to a HZE particle track 10 cell diameterslong with LET > 200 ReV/pm in its core and > 25 rad dose in its penumbra at a distance of10 Urn, then the microlesion dose rate in geostationary orbit, for example, is about 9,000microlesions per cm

3 of tissue per month.

INTRODUCTION

Earlier western writings on the general subject of space radiation safety dealt withastronauts in Earth orbit or lunar trajectories as a special—risk group [1, 2]. Thepossibility of constructing orbiting space stations introduces the need to consider spaceradiation risks in terms of larger populations, possibly a few thousand people over periods

of a few years [31. Since labor will have to be performed outside the shelter of a spacevehicle the charged particle hazard is higher than that expected or experienced by tradi-tional astronauts.

In contrast to the low—Earth orbits customarily used in manned orbital flight, high orbit(e.g. geosynchronous) vehicles encounter high radiation dose rates in the Earth’s trappedradiation belts. Trapped electrons are distributed in the inner zone at about 2.8 Earthradii and in an outer zone which extends beyond this distance but has a variable maximumposition that depends on solar magnetism. Geostationary vehicles encounter the outertrapped’ electron zone, as their altitudes are beyond the slot” (at 2—3 Earth radii)

between’~the two zones. Protons are also distributed toroidally around the earth, but thereis no proton “slot, and proton flux is substantial in low—Earth orbit [4] where protonsdominate the particle dose——especially behind 1.0 or more g/cm2 shielding. In geosynchro-nous orbit trapped high—energy proton fluence can be neglected in dose calculations [5]as it decreases by several orders of magnitude beyond about 3000 km, where it is maximal[6]. It is clear that there is no greater contributor to the constant physical dose ingeosynchronous orbit than the trapped electrons and the bremsstrahlung they produce uponinteraction with the matter of the space vehicle.

Although trapped electrons are the greatest constant hazard, high—energy solar particleevents can occur near the beginning and end of periods of maximum activity in the 11—yearsolar sunspot cycle. Solar storms are normally considered to consist of protons, butthey contain other particles as well, especially carbon, nitrogen, and oxygen. As anextreme example, the most intense series of solar particle events of solar cycle 19occurred in July 1959, and it has been estimated that in 4 days it delivered a total akindose, behind 1 g/cm2 shielding, in excess of 1000 rads. Nearly half of this dose wasdue to alpha particles and about 3% to C, N, 0, and fluorine nuclei [7]. In a sense,

solar particle events are also to be considered as a source of high—Z energetic (HZE)particles. In the event just mentioned, if a quality factor of 10 is assumed, a dose of30 rem would have been delivered by the solar HZE particles alone. These calculationswere made for a lunar transfer trajectory.

187

188 P. Todd

Geosynchronous orbit lies within the Earth’s magnetosphere, so lower energy particleswould be deflected, and a corresponding reduction in solar particle dose would occur.However, solar HZE’s seem to occur in solar particle events that have a “shallow rigidity

spectrum”—in other words events in which up to 5% of the particles have energies above 100MeV/nucleon [7]. Stassinopoulos [5] estimates that a 90 day visit in geosynchronous orbitduring which one anomalously large solar particle event occurs would result in exposureto a total fluence of about 7 x 108 solar particles/cm

2 this could presumably include up

to 3 x l0~ solar heavy particles of energy greater than 100 MeV/nucleon.

Most of the constant HZE dose comes from the galactic cosmic radiation, and these particlesare the principal subject of this report. Madey [8] estimates that, in geosynchronous orbitat solar minimum, the flux of ions with atomic numbers falling between Li to Ni adds up toabout 20 particles/m2—sec—sr or about 60 particles/m2—sec in 2u exposure geometry. Forcomparison with the above solar particle fluence, this amounts to 5 x 1O particles/cm2

having energy greater than 1.4 GeV/nucleon. A very rough estimate, based on a powerfunction spectrum using 1.5 as exponent converts this to about 3 x 106 particles/cm2having energy greater than 100 MeV/nucleon. It thus appears that under certain solar con-

ditions galactic and solar HZE particles could have comparable contributions to the dose.An important difference between the solar and galactic HZE particles appears to be thefraction of particles with Z greater than about 20. These particles are less than 1% asabundant as ozygen nuclei in solar particles [9] and more than 20% as abundant as oxygennuclei in galactic cosmic rays [8]. More particles heavier than Ne occur in the galacticradiation in 90 days than in the solar radiation during high—dose events——about 6 x l0~vs 3 x l0~ particles/cm2 in 90 days, respectively.

Madey [8] has said, in part, “There is a major uncertainty in the assessment of theradiation hazards because of the lack of information on the biological effects of the HZEparticles. There is a need to monitor exposure to HZE particles because of the unknownbiological effects from the unique type of injuries produced by these particles.” Thisreport, therefore, attempts to synthesize some of the available information on the

biological effects of HZE’s and indicate the Status of knowledge and possible means ofapplying it to problems encountered in deep space flight. Although not detailed here, asimilar approach is applicable to strongly—interacting particles, which produce showersof HZE particles. This subject has been studied by Akoev and associates [10].

HZE PARTICLES

All particles with Z greater than 2 are considered HZE’s, and energy definitions vary, butmost discussions consider particles having more than 50 MeV/nucleon. By these definitionsthe total flux density of galactic HZE’s is 0.05 particles/cm2—sec [7].

The HZE component of the galactic cosmic radiation is not greatly reduced by reasonableamounts of shielding, although the He com~onent can be reduced about 40% by the first1 g/cm2 aluminum. A thickness of 10 g/cm aluminum is about 1 collision mean free pathfor ions from Ne to Fe, but nuclear collisions result in fragments at least one of which

will always be another HZE. Due to the high energy nature of the galactic particle spec-trum 10 g/cm2 aluminum attenuates the HZE dose by only 25—40%, depending on the particle[11].

If one considers only particles with LET greater than 100 ReV/pm, however, calculationsindicate “a decrease from 7.8 to 2.6 ions/cm2—hr . . .as the shielding increases from 1 to10 g/cm2 aluminum.” Of these ~articlea, 65% are in the za 20 range [12]. Space—suit

shielding, typically 0.16 g/cm , has essentially no effect.

HZE particles interact with matter in obedience to the Bethe—Bloch energy loss formula;they not only produce energy losses at high LET, but they also produce high energy

secondary electrons, thereby producing a broad (more than 10 pm) “delta—ray penumbra.”This fact is perhaps best summarized by a diagram by Magee and Chatterjee [13) reproducedas Figure 1. It indicates substantial doses at large radii (comparable to cellular dimen-sions) from the particle track core. HZE particles also fragment when they interact withnuclei, thereby increasing the dose per particle.

Multiplication of the HZE dose by a quality factor (QF) or correcting individual particledoses by a QF increases the rem dose substantially. In single human cell experiments re-

lative biological effectiveness (RBE) values greater than 10 have not been observed, evenat the lowest doses tested. Also, single—cell RBE decreases with increasing LET aboveabout 200 Key/pm [14]. If one assumes QF = 10.0 for the total galactic cosmic ray dose,then, for example, 18 rem/90 days due to HZE’s in geostationary orbit increases by 30—50% the expected trapped—electron and bremsstrahlung dose of 30—50 rad.

Biological Aspects of Space Radiation 189

lo9g i lii,l~ I TITIIIJ I Till!

1

F NEON PARTICLESEnergy (MeV/n) LET(keV/u) Core(s) Penumbra(~)

lo8 — ~ 300 35.5 67.3 I.23x106

E (B) 215 43.3 601 8.98x105D (C) 100 73.6 44.2 3.94xI05

F (0) 50 125.9 32.4 I.7x io~IO~ .—.(E) 43 142.1 30.2 l.41x105

E C (F) 10 466.9 15.0 2.ItXlO4A

0 —oC

8 —

AF

0’ -

E

IO~ B

102 I liii I I III I I I 1111102 l0~ 100 10

Rodiol distonce (IL)

Fig. 1 Log—log plot of calculated energy density versus radial distancefrom neon particles passing through water (from Magee and Chatterjee, 1977).The core and penumbra regions are separated by a one—to—two—log unit step inenergy density. The energy density of the core is shown as uniform whilethat of the delta—ray penumbra region decreases with radius. The radius of

the core and penumbra increases with particle energy. Reproduced withpermission [13].

More useful than rad dose in HZE particle dosimetry, however, is the particle fluenceand its LET distribution. Several biological end—points, such as mammalian skin effects,

plant abnormalities, human cell killing in vitro, and developmental abnormalities havebeen characterized on this basis [12, 14]. Information on particle fluence and LETdistributions in space radiation fields is obtained from the integral—number LET spectra

(fluence vs. threshold LET) for the major HZE particles at solar minimum under noshield-ing (Maximum—flux conditions), as prepared by Curtis [15], for example. Fe (Z =

26) nuclei are responsible for practically all of the total dose delivered at or above

200 KeV/pm. This fact is not surprising in view of the importance of Fe nuclei in thegalactic cosmic radiation. The total particle flux is a few (1—10) particles/cm2—min,whereas the total particle flux above LET 200 Rev/pm is about 2 particles/cm2—hr.

The most significant feature of HZE particles is their ability to inactivate several cellsby the energy deposited by a single particle. This fact makes such concepts as absorbeddose, RBE, and Quality Factor almost impossible to use in assessing the biological hazardsassociated with these particles. Therefore, when small groups of cells are at risk, theeffectiveness of HZE particles is very high [16, 17]. When a particle loses energy intissue as described in Fig. 1, the physical event is sometimes called a “thin—down” hit,and the corresponding biological event a “microleaion.”

A microlesion is defined as a region of focal cellular destruction caused by the passageof a single HZE particle. The microlesion is suggested as a biologically relevant unitof radiation damage for the purpose of assessing the hazard of radiation fields in mannedspace travel. Research on the extent of functional impairment or carcinogenesis in

critical tissues as a function of microlesion density is recommended. Some examples ofmicrolesions on which a certain amount of biological research has been done are presented

below.

190 P. Todd

THE MICROLESION CONCEPT

Hair Follicle Effect. Although the hair follicle is not generally considered a vitalorgan, it was the first tissue in which the exceptional effects of cosmic radiation werediscovered. When black mice returned from balloon flights and developed a few grey hairs[16] it was concluded that all of a tiny number (a dozen or so) melanocytes surrounding thedermal papilla at the base of the follicle were inactivated by a single HZE particle;however, a role of indirect effects (due to radiation damage elsewhere) has also beenexplored [18]. It has been suggested [12] that microlesions require a critical orthreshold ionization level.

Fe,Z~26 Z-.=90

k cX~f10 A ~~‘~I Ic) ~\

d ~

‘~c~,9J501u.m

IO~m

Fig. 2 Diagrammatic representation of HZE tracks and a cluster of cells atthe same magnification. The track on the left, traced from a track—emulsion

photograph represents the path of an iron nucleus, showing the track core(straight thick line) and very large delta ray spurs (irregular dashed lines)

and blobs (near the track). The diagram on the right represents the trackleft by an ultra—heavy nucleus in the same emulsion; the shaded area representsthe track ‘core”, which is surrounded by very dense delta—ray blobs.

Physical Requirements for Microlesion Production. The microlesion concept can be visualizedin Fig. 2, which compares the dimensions of an iron nucleus track with those of typicalmammalian cells. Because the LET is above 200 ReV/Urn all along the track, all cells whosenuclei are struck will be inactivated. In addition all cells in the delta—ray penumbrareceive a high dose of low LET electrons to their nuclei, 25 rads to se-.’eral hundred rads.The ultra—heavy ion track also displayed diagrammatically in Fig. 2, can be imagined, onthe same magnification scale, to inactivate yet more cells per unit path length, owing tothe greater dimensions of both the core and penumbra. Above a certain critical ionizationlevel, therefore, a core of dead cells will be surrounded by some non—lethally damagedcells. The critical ionization level required to produce a microlesion that has an impacton a tissue will vary from organ to organ, and it ia not quite correct to consider the

microlesions as an all—or—nothing phenomenon.

Biological Aspects of Space Radiation 191

“CORE SI~ LET > 200 keV/pm VDELTA ‘~‘ D>25RAD I / lOjimRAYS _______________ A.

4 ~IOCELLS

Fig. 3 Diagrammatic representation of a segment of a HZE track that qualifiesas a microlesion event. In this particular case, a minimum track core LET of200 Key/pm and a delta—ray dose of 25 rad out to 10 pm radially are requiredover a distance of 10 cell diameters. The configuration of energy depositionrequired to produce a microlesion is expected to differ from tissue to tissue.

With these reservations, it is suggested that a “typical” critical ionization level shouldconsist of a charged particle with total LET exceeding 200 ReV/pm over a distance corres-ponding to at least 10 cell diameters from the primary particle trajectory. This de-

finition is described geometrically in Fig. 3. This definition of the microlesion eventhas biological significance in that the chosen minimum total LET leads to a probabilityof nearly 1.0 that the cell whose nucleus is struck will be inactivated [17]. A pen-umbral dose of 25 rad of low LET radiation is known to inactivate more than one humancell in 20 [19].For example, neon ions are apparently the lowest—Z particles to fulfillthe criterion given in Fig. 3 since the penumbra dose remains above 25 rad out to at

least 7 pm as the particle energy falls from 20 to 10 MeV/nucleon and the LET exceeds200 ReV/pm (Fig. 1) [13]. At least 20 cells are inactivated with nearly 100% probability[17].

Incidence of Microlesions. By adhering to the critical ionization definitions givenin Fig. 3, the flux of particles capable of producing microlesions can be determined froman integral LET spectrum of a given space radiation environment.

5ui’0

‘~‘I0CELL DIAMETERS

IOo~5~~:3o

Fig. 4 Path length of MZE particles in tissue for various LET thresholds in

ReV/pm in tissue (adapted from Grahn, 1973). The ares outlined in the upperright is the microlesion region, based on the definition of Fig. 3. Allparticles below the LET > 230 ReV/pm curve and above the 10 cell—diameter (300 pm)threshold are capable of producing microlesions. No particles with rangebelow the LET = 2500 KeV/c curve produce microlcsiona unless Z > 30.

192 P. Todd

Figure 4 is a plot of the path length over which a particle deposits energy above acritical LET [12]. Since it was estimated above that Ne is the minimum ion and 200 ReV!pm is the minimum LET to produce microlesions, and 10 cell diameters (taken as 300 pm)is the length of a microlesion, a microlesion envelope is drawn on the figure. If all of

the stopping events are considered to be due to Fe alone, the graph indicates that themaximum critical path length is about l0~ pm or about 300 microlesions per Fe particle

stopping (without fragmenting). The “dose” of microlesions accumulated after 90 days ingeostationary orbit, for example, would be 27000 microlesions per cm

3 of tissue. Thisvalue represents an upper limit, as not all particles are Fe nuclei with lO~ pm stoppingdistance in tissue. This microlesion dose inactivates less than 0.1% of the cells,assuming about lO~ cells/cm3, the same cell killing effect as about 0.4 rad of gammaradiation [19].

In terms of cell killing, it would appear that HZE’s are less effective than gammaradiation. This fact is expected for two reasons. More energy is deposited by HZEparticles in cell nuclei than is required to kill the cell; the energy is localized anddoes not reach out to live cells anywhere except in the path of the particle. Since thecell—killing effectiveness of HZE particles is not exceptional, the biological effects ofmicrolesions in various tissues constitute the principal unkown in HZE particle radio—

biology.

BIOLOGICAL EFFECTS OF MICROLESIONS

Hair Depigmentation. Quantitative studies on hair depigmentation have led to the con-clusion that the passage of a single nitrogen ion can prevent the function of all of themelanocytes at the base of the follicle [20]. This laboratory finding confirms theearly studies in which mice were exposed to cosmic rays at the top of the atmosphere [16]

and supports the validity of the microlesion concept as it applies to this endpoint,irrespective of its relevance as a health hazard.

Effects of HZE Particles on the Retina. Several astronauts have reported seeing lightflashes during lunar excursions, and laboratory experiments have confirmed that one ofthe mechanisms inducing this phenomenon is the passage of HZE particles through the re-tina. The exposed human retinas are not available for subsequent investigation forpathological and functional changes, but physiological and histological studies havebeen performed on carbon and neon ibn—irradiated retinas of the mudpuppy Necturusmaculosus and C57B1 mice [21]. The effects of 50 rad of Ne ion irradiation indicatemorphological damage to inner and outer segments of rods and cones and to their inter-connections. Similarly, cells of the neural cell layer were found to be morphologicallydamaged. It is thus expected that passage of a single HZE particle will affect more than

one retinal cell.

Damage to rod outer segments alone has been found to be partially repaired by the naturalprocess of disk replacement, but disorder in the organization of disks seems to persist.

The manifestations of such damage over periods of years have not been studied.

The Lens of the Eye. The lens itself might be expected to experience about 5 x 10’ HZEparticle hits per 90—day mission, of which some 5% meet the microlesion criterion of Fig.

3. It remains to determine the probability of opacification per microlesion. If thisprobability were, for example, 10 2 then about 50 potential opacification sites permission per worker would be predicted. In any case it appears that the cataractogenicpotential of the deep—space radiation field could be quite high.

Tumors in Model Systems. Irradiated Arabidopsis seeds give rise to plants with tumors.The maximum RBE for this end—point is about 35—50 when C, Ne, or Ar ions are used [20].

Tumors have not been reported in plants germinated from similarly—irradiated maize seeds.

It was previously noted [12] that the microlesion has no counterpart in medicine. Itmight be possible, nevertheless, to understand the carcinogenic potential of microlesionsin terms of studies on pulmonary carcinogenesis by alpha—emitting particulates. A fewdozen alpha decays per particulate have the effect of killing alveolar or endothelialcells at the ends of the alpha particle tracks, while delta rays and the sparsely—ionizingsegments of tracks are capable of inflicting nonlethal genetic damage. In the context

of the two—step theory of carcinogenesis the genetically damaged cells would be “initiated”and the killed cells, which would need to be replaced, would be considered “promoters”

(of multiplication of the damaged cells). The distribution of radiation from alpha—emit-ting particulates is known to induce pulmonary cancers, and this analog is noteworthywhen considering the carcinogenecity of microlesions. One kilogram of lung tissue mayreceive several million microlesions per deep—space mission. The carcinogenic risk willtherefore depend on the probability per microlesion of inducing a malignant focus. Thisprobability remains to be determined in laboratory experiments.

Biological Aspects of Space Radiation 193

Central Nervous System. Early concern developed over the possible neurological effects ofHZE particles, and space experiments have been designed to seek tracks in brain tissuesof mice. Stopping alpha particles may have RBE5 as high as 30 for impairment of axonalconduction, so concern for CNS damage persists [20]. In most cases, the inactivation

of 0.1% of the neurons in a given part of the brain would not be considered serious, andsome regeneration can occur, but some critical nuclei in the brain contain a small numberof cells with highly specific function; such cells are heavily protected by glial cells,which could be damaged along with their nerve cells in a single microlesion.

Critical Tissues. Although HZE particles deposit energy in an inefficient way, they alsocause a unique distribution of biological damage that could lead to poorly predicted

biological sequelae. “Dose” is perhaps better measured in microlesions/cm3 rather than

in rads.

It is certain that HZE particles will lead to no functional decrement in critical tissuesduring a mission. Only later effects requiring the expression of tissue damage can beexpected. Very small decrements in visual acuity might result from damage to cones andganglion cells of the fovea centralis, and late cataracts could develop. Outside theeye, there are no clear indications of anticipated lesions causing physiological de—crements, but the effects of microlesions on small nuclei of the brain need to be

evaluated.

There are reasons to believe that microlesions might be carcinogenic in lung, the organin which comparable events have been investigated.

FUTURE DIRECTIONS

Studies of the effects of HZE particles on structures of the eye are under way [21], andthe unique developmental effects of HZE particles have been characterized in a limitednumber of systems [20]. The neurological effects of HZE microlesions can now be morecarefully characterized in experiments using accelerated beams of Fe ions and modern

histochemical techniques. Pineal or pituitary function in the pocket mouse might besuitable physiological indicators of microlesion effects, since these organs are verysmall, and their functions are readily analyzed. Hepatocarcinogenesis and pulmonarycarcinogenesis experiments in Fe ion irradiated laboratory animals should be productive,since the lung and liver seem to be responsive to the carcinogenic effects of microlesion—like damage.

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