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LUNG CANCER INCIDENCE IN THE CZECH REPUBLIC IN 1970-1990. M. Marel, L. Melfnova, Z. Sk&xl, J. Krenarova, R. Marelova. Pneumological Clinic of Charles University Prague 6,Csech Republic/CR/

The authors collected data about Lung Cancer/LC/ inci- dence from three sources.From the National Oncological Register for the CR/about 10 milion people/,from the Uni- versity Pneumological Clinic with a catchment area of 1 milion people,and from the district pneumological centre covering the area with 44 000 inhabitants.The incidence of all malignant tumor in CR in absolute number of patients increased from 29 774 in 1970 to 44 713 in 1990.The inciden- ce of LC in this period increased from 88,3/100 000 to 99,6 1100 000 in men and from 8/100 000 to 16/100 000 women. A different development of incidence was found in region with and without haevy industrial pollution.In the non-in- dustrial South Bohemia region the absolute number of LC in the 20 years period decreased from 491 to 461 cases,but in Nothern Bohemia with the coal and chemical industry it increased from 618 to 768 cases.The number of diagnosed patients with LC in the University Clinic did not signifi- cantly change and was slowly decreasing from 227 new patients in 1970 to 207 in 1990.The percentage of patients submitted to surgery declined from 45% to 18% in this pe- riod.The most frequent type of cancer was squamous one, the small cell LC was slowly increasing from 15% in 1970 to 26% in 1990.In the district department of pneumology in central Bohemia LC incidence slowly declined from 38 cases in 1970 to 21 in 1990

On the basis of this data the authors consider that in 1979-1984 the incidence of LC in the CR reached its peak and at present it is mooving in the plateau part of the incidence curve.The influence of industry and chemi- cal pollution to the incidence of LC requires further study.

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MUTAGENIC EFFECT OF CYTOSTATIC THERAPY ON CHROMOSOMES OF PATIENTS WtTH LUNG CARCINOMA V. KaEar-Kukrid, G. Radosavljevi&sid, Institute for Lung diseases, Belgrade, Serbia.

We studied the incidence and importance of chomosomal aberrations (ChrAb) in 31 pts with bronchial CA (25 SCLC and 5 AdenoCA) receivin chemiotherapy (CT) only, according to CAV (C iOOOmglrc2, A 80m /m V Imglm2-Dl) , and FAM protocol (5Fu 500mg, 01-5. A Dl 8Omglm s4 and M 9mg D5) in intervals of 4 weeks. All subjects were smokers, exposed to X-rays only during the diagnostic procedure, with no signs of viral infection. Cytogenetlc analysis (CgA) of chromosomes in the peripheral blood was performed using G-bands and Morrhead method. The total of 9300 cellular metaphases were examined, 100 per patient averagely. In the grp of 20 pts (SCLC and AdenoCA) three CgA per pts were performed 28 days after the CT course, while in 11 pts (SCLC) the study was performed 24, 48 and 72 hrs after the first CT. RESULTS: Chromosomal lesions were recorded in 71 pts. Great variability of cytogenetic ehect of CT was noted. The higest percentage of ChrAb was noted 72 hrs after CT (CAV) - 3.09%. The same CT for the following 3 months did not lead to increase of number of cells with ChrAb The means values of all findings were significant (p<O.Ol), as well as distribution of these findings in % in-the studied intervals with permanent increasing trend fmonotonv trend test Zf=4.094). The incidence and level of cells with ChrAb after 1 CT differed significantb from the subsequent findings (Tl:T2<0.05, Pf=O.O129. Tl:T3<0.05, Pf=O.O0519). The changes were most common seen in the chromosomal structure (98%). The incidence of breakage and chromosomal lesions before and after CT did not differ significantly, while the significance was reached in dyscentric and ring chromosome counts at 72 hrs after CT vs. pre-therapy results. Only two numerical ChrAb (polyploidia and endoreduplicatton in 2 cells) and 1 cell with 2 identical ChrAb (2 ring chromosome) were found after 2 CT. CONCLUSION: ChrAb are caused by CT in pts with bronchial CA and are of utmost importance in younger pts in reproductive period of life. Determination of the risk of real genetic lesions necessitates continuous monitoring in months after CT. The method is not convenient for routine practise. These investigatons are also important for estimations of risk of occurrence of induced CA and they also contribute to study of drugs used for immune suppression.

Genetic polymorphism of CYP2D6 and Lung Cancer Risk. G. L. Shaw, B. Weiffenbach, R. T. Falk, J.N. Frame, J. C. Nesbitt, H. I. Pass, N. E. Caporaso, R. N. Hoover, D. T. Moir, M. A. Tucker. National Cancer Institute, Bethesda, MD, National Naval Medical Center, Bethesda, MD, and Collaborative Research Inc., Waltham, MA.

Previous reports of the association of extensive debrisoquine metabolism, controlled by the cytocbrome P450 CYP2D6, with increased lung cancer risk have been conflicting. We examined the hypothesis that the genetic polymorphism of debrisoquine metabolism identities individuals at increased risk for lung cancer in a case-control study of 116 incident Caucasian lung cancer patients and 114 age, race and sex matched controls conducted at the National Naval Medical Center, Bethesda, MD. Polymerase chain reaction techniques at the CYP2D6 locus detected mutations identifying the A, B and J alleles, and restriction length polymorphism analysis was used to detect deletion of CYP2D6. Stratified and unconditional logistic regression analyses were used to evaluate the association between homozygous wild type extensive metabolizers, heterozygotes, and homozygous deficient metabolizers and lung cancer risk. No excess risk was observed among extensive or intermediate metabolizers, with odds ratios less than 1.0. The lack of an effect could not be explained by smoking, stage or histology of lung cancer. While the concept that polymorphisms of metabolism may account for differential susceptibility to lung cancer is sound, these data do not support the role of CYP2D6, defined by the alleles we examined, as a marker for lung cancer risk.

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SERUM ANTI-BENzo(a)pyRENE DIOLEI’OKIDE-DNA ANTIBODIES IN ‘IWE GENERAL POPDLATION. S. Petruazelli, A. Celi, N. Pulerh, F. Baliva, L.M. Tavanti, P. Paoletti, G. Viegi, C. Giuntini. Respiratory Pathophysiology Unit and CNR Institute of Clinical Physiology, Pisa, Italy.

Biomonitoring of genotoxicants in human cells or fluids is gaining attention in epidemiologic studies on the effects of pollutants on human health. Tobacco smoke is a mixture of widespread potential carcinogens, such as benao(a)pyrene, both in the outdoor and indoor environment. Seven hundred ninety-six individuals from a general population sample were studied for the presence of serum antibodies against benzo(a)pyrene diolepoxide. Subjects underwent a standardized questionnaire and peripheral venous blood sampling. Age, sex, present and past smoking habit were recorded for each subject. Blood samples were tested for antibodies against benzo(a)pyrene diolepoxide-DNA adducts (Ah-BPDE- DNA) using a modified version of Newman’s ELISA method (J Clin Invest 1988; 82: 145-153). BPDE-DNA was synthesized and chemical identity was verified by HPLC and UV spectrometry. Individuals were classified as positive or negative for Ab-BPDE-DNA by comparison with binding to nonmodified DNA. Subjects were considered as smokers if they smoked within the last six months. One hundred twenty-two subjects (15.3%) had serum Ab-BPDE-DNA; the prevalence of positive subjects was higher in smokers (20.4%) than in nonsmokers (14.1%, pcO.05). However, no differences could be found between exsmokers and individuals who had never smoked (14.1% and 13.8%, respectively). In smokers, no associations could be found between presence of Ab-BPDE- DNA and cigarettes smoked per day. Individuals with Ab-BPDE-DNA were older than the others (4ti17 yrs us 41f17 yrs, p<O.O2), and this effect was still present aRer adjusting for smoking habit. These data suggest that the presence of Ab-BPDE-DNA may be a marker of DNA damage due to recent tobacco smoke exposure and that older people may be more susceptible to the genotoxic effects of tobacco smoke.