233

response rate of the VP combination was low compared with CDE (83%) and IMP (77%). Toxicity of all three regimens was acceptable.

and dose reduction for mydosuppression was necessary in only a mmority of the patients. We conclude from this study that dtecombirta- lion of carboplatin, at the maximally tolerated dose of 400 mg/m2, in combmation wtth ifosfamidc 5 g/m2. is an active regimen with efficacy comparable with the standard CDE regimen.

A nested case-control study of lung cancer among silica exposed

workers in China

McLaughlin JK, Jing-Qiong C, Dosemeci M, Rong-An C, Rexing SH, Zhien W et al. National Cancer Ins~irute, EPN-415, Befhesda, MD

20892. Br J lnd Med 1992;49:167-171. In an attempt to assess whether silica induces lung cancer, a nested

case-control study of 3 16 male lung cancer cases and 1352 controls was carried out among pottery workers and tungsten, copper-iron, and tin miners from five provinces in south central China. Exposure todust and silica for each study subject was evaluatedquantitatively by cumulative exposure measures based on historical industrial hygiene records. Measurements on confounders such as inorgantc arsenic, polycyclic aromatic hydrocarbons (PAHs), and radon were also collected from the worksites. Information on ctgarette smoking was obtained by inter- views of the subjects or their next of kin. A significant trend of increasing risk of lung cancer with exposure to silica was found for tm mmers, but not for mmers working in tungsten or copper-iron mines. Concomitant and highly correlated exposures to arsenic and PAHs among tm miners were also found. Risk of lung cancer among pottery workers was related to exposure to silica, although the dose-response gradient was not significant. Risks of lung cancer were siguificantly increased among sihcotic subjects in iron-copper and tin mines, but DOI in pottery factories or tungsten mines. The results of this study provide only limited support for an aetiological assoctatton between silica and lung cancer.

Asbestos exposure, asbestosis and lung cancer

Lehnert G, Raithel HJ, Valentin H. lnstirutfur Arbeirs- und Sozialme-

dim, Universitat Erlangen-Nurnberg, Schillersrr. 25 + 29,852O Er-

fangen. Arbeitsmed Sozialmed Praventivmed. 1992;27:96-101. Asbestos-related malignancies are one of the mam topics in the

occupational medical arid socml political discussion. The numbers of asbestos-induced mesotheliomas (No. 4105) as well as lung cancer in connection witlr asbestosts or asbestos-related lesions of the pleura (No. 4104) have been significantly increased in the last years. Whereas the causal relation between asbestos-exposure and asbestosis as well as the mesotbelioma is defmitely proved epidemiologically the question whether asbestos can cause lung cancer without asbestosis or asbestos related lesions of the pleura is disputable till now. Referring to this topic the mtemational literatureis reviewed. In synopsis there areno unequivocal mdications that an mcreasing number of isolated lung cancer diseases could be observed. So it is our opinion that the admission of ‘asbestos- -related lung cancer’ (withoutasbestosis or asbestos-induced lesions of the pleura) m the list of occupational diseases can’t be recommended.

Basic biology

Cigarette smoke-induced DNA damage in cultured human lung

cells: Role of bydroxyl radicals and endonuclease activation

Lcanderson P, Tagesson C. Depanmen~ of Occupamnal Medkne.

Facully of llealrh Scwms, S-WI 85 Lmrloprng. Chcm-Biol Interact 1992;81:197-208.

Cigarette smoke can cause DNA single strand breaks m cultured human lungcells(T. Nakayamaetal., Nature, 314 (1985)462-464) but the mechamsms behind this DNA damage have not been clearly elucidated. In thepresentstudy we have investigated thcposstbihty that one of the major constituents m cigarette smoke. hydroqumone. may bc

important for mediating smoke-induced DNA damage m die human epithelial lung cell line, A 549, and the mechamsms behind this damage. Cells were exposed to cigarette smoke, hydrogen peroxide, or hydroquinone, in the absence and presence of different mhibitors, and the resulting DNA damage was assessed either as DNA smgle strand break formation or formation of the oxidative DNA adduct, 8-hy- droxydcoxyguanosine. It was found that (i) exposure 10 cigarette smoke, hydrogen peroxide or hydroqumone causes a rapid decrease in the intracellular thiol level andaconsidcrablc DNA single strand break formation, (ti) the formation of DNA single strand breaks m cells exposed to cigarcttc smoke is mhibited by catalase, dimethylthiouma and o-phcnantroline, suggesting that hydroxyl radicals generated from iron-catalyzed hydrogen peroxidedissociauon are involved m the DNA damage, (iii) hydroquinone causes considerable DNA strand break formation that is blocked by aurmtrtcarboxyhc acid, an mhibitor of endonuclease activation, and by BAPTA, an intracellular calcium chelator, (IV) addition of hydroqumone to a smoke condensate greatly enhances its ability to cause DNA single strand breaks, and (v) smoke, but not hydroquinone,causes formation of 8-hydroxydeoxyguanosine, a DNA damage product induced by the action of hydroxyl radtcals on the DNA base, deoxyguanosine. These findmgs suggest that the abihty

of cigarcttc smoke to cause DNA smglc strand breaks m cultured lung cells is due to mechanisms involving hydroxyl radical attack on DNA and endonuclease activation. They also suggest that hydroqumonc is an important contrtbutor to the DNA damagmg effect of cigarette smoke on human lung cells.

Assay for type III collagenolytic activity in lung cancer tissue

Kawamura M, Kato R, Kikuchi K, Kobayashi K, Ishihara T, Shibata T et al. Departmem of Surgery. Keio University. School of Medtcine.

Tokyo 160. Clin Chim Acta 1991;203: 225-34. WC developed a method for measuring the activity of type III

collagenolytlc enzyme in lung cancer tissue, using as substrate, type III collagen purified from human placenta. In this method [3Hlpropionate is used for labeling type III collagen, with bacterial collagcnase used for making the standard curve. It, therefore, becomes possible to compare type III collagenolytic activity with those of other collagen subtypes (lypcs I and IV). As this method is a fibrd assay it is not susccptiblc to trypsm or other proteases. The average type III collagcnolytic cwymc activity was higher in squamous cell carcinoma than m adenocar- cmoma, while that of lung cancer tissue exceeded that of normal lung tissue. The activity of type 111 collagenase mcrcased with the progrcs- sion from one disease stage to the next.

Tumor-antigen-specific humoral immune response of animals to

anti-idiotypic antibodies and comparative serological analysis of

patients with small-cell lung carcinoma

Lehmann H-P,ZdwxkyC, Warbcl R, Sahel RA.D~won ofOnc&qy.

Deparmm of Medicine. University Ilospiml, CH-8044 Zurrch. Int J Cancer 1992;50:86-92.

We have prevtously developed 3 monoclonal am-idiotypic antibod- ies (Ab2) of LOU rat origm directed against the bindmg site of the murine monoclonal IgM LAM& which recognizes the small-cell lung carcinoma (XIX)-associated sialoglycoprotem anttgen sGP,, ,~(. The aim of this study was to compare the efficicncics of these 3 Ab?.

designated LY8-229, LX%531 and LXX-632, to mducc anugcn-spe- cific imunity in different animal species without prior exposure of the recipients lo the nominal antigen, and thereby possibly select an Ab2 candidate for active Immunotherapy against SCLC m pattents. The

feasibdlty of tbisapproach was furtherevaluated by a serological analy-

sis of patients with SCLC compared with healthy mdivlduals, m whom

the spontaneous antibody reactivities agamst SCLC ccl1 lmes and Ab2 were tested. LY8-229 was shown to be me most effect Ab2 m mducmg anllgen-specific antibodies rn BALB/c mice, CBA/J&r mice arid one NZW rabbit. Furthermore, LY8-229 was the only Ab2 agamst which

slgmf~cantly elevated idiotype-specific antibody reacuviues cxislcd m