The modulation of benzo[a]pyrene diolepoxide (BPDE)-DNA adduct levels by polymorphisms in the CYP1A1, GSTM1 and GSTT1 genes was assessed in leukocytes of Caucasian males. Eighty-nine coke oven workers (35 smokers, 36 ex-smokers and 18 non-smokers) were recruited from job categories with different exposure levels to polycyclic aromatic hydrocarbons (PAH), together with 44 power plant workers (all smokers) not exposed to PAH. BPDE-DNA adducts were detected in 69 of 133 (52%) DNA samples with a 100-fold variation (range 0.2-44 adducts/10(8) nt) and a median of 1.6 adducts/10(8) nt. All samples with the GSTM1 active genotype (n = 59) and five out of 74 samples with GSTM1*0/*0 (7%) showed non-detectable adducts (<0.2 adducts/10(8) nt) and 69 of 74 subjects with GSTM1*0/*0 (93%) had detectable adducts (>0.2 adducts/10(8) nt). The difference in adduct level between the GSTM1*0/*0 and GSTM1 active genotypes was highly significant (P < 0.0001). No significant difference in adduct level between the GSTT1*0/*0 and GSTT1 active genotypes was seen. All heterozygotes (CYP1A1*1/*2) from subjects of GSTM1 active type did not have detectable adducts. Among the GSTM1-deficient individuals (n = 69), 42 with the CYP1A1*1/*1 genotype showed a lower adduct level (median 1.3, range 0.2-4.1 adducts/10(8) nt) compared with 26 individuals with heterozygous mutated CYP1A1*1/*2 genotypes (median 2.5, range 0.4-6.1 adducts/10(8) nt, P < 0.015). One individual with low PAH exposure and the rare combination CYP1A1*2A/*2A-GSTM1*0/*0 showed an extremely high level of 44 adducts/10(8) nt. Significant differences in detectable adduct levels were found between the CYP1A1*1/*1 and CYP1A1*1/*2 genotypes in the exposed group low + medium (P = 0.01) and for all adduct levels, detectable and non-detectable (set at a fixed value), in highly exposed individuals and in ex-smokers (P = 0.03), whereas no such differences were observed in the control group. Mutated CYP1A1*1/*2 increased the adduct level in non-smokers from the exposed group (1.4 versus 2.2 adducts/10(8) nt), but had no effect on the smokers from the exposed group (2.3 versus 2.8 adducts/10(8) nt). When all variables were dichotomized, statistical evaluation showed that CYP1A1 status (P = 0.015), PAH exposure (P = 0.003) and smoking (P = 0.006) had significant effects on adduct levels which increased in the order: CYP1A1*1/*1 < CYP1A1(*1/*2 or *2A/*2A); environmental exposure < occupational exposure; non-smokers < smokers, whereby adducts increased with cigarette dose and the duration of smoking. Higher levels of BPDE-DNA adducts in individuals with the combined CYP1A1(1/*2 or *2A/*2A)-GSTM1*0/*0 genotype suggest that these genotype combinations are at increased risk for contracting lung cancer when exposed to PAH.

The level of (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) bound to DNA of lymphocytes plus monocytes in 39 coke oven workers exposed to polycyclic aromatic hydrocarbons (PAH) and 39 non-exposed persons (controls) were investigated, each of the groups consisting of smokers and non-smokers. The adduct level was measured by an improved HPLC/fluorescence method (Rojas, M., Alexandrov, K., van Schooten, F. J., Hillebrand, M., Kriek, E. and Bartsch, H., Carcinogenesis, 15, 557-560, 1994) through the release of the corresponding benzo[a]pyrene (B[a]P) tetrols. The anti-BPDE-DNA adduct was detected in 51% of coke oven workers exposed to PAH and in 18% of the non-exposed (control) subjects. The mean level of anti-BPDE-DNA adducts/10(8) nucleotides in coke oven workers (15.7 +/- 37.8) was approximately 8 times higher than in non-exposed subjects (2.0 +/- 8.7). The interindividual variation of adduct levels was approximately 100-fold in coke oven workers and approximately 50-fold in controls respectively. Smokers in the exposed group had 3.5 times more DNA adducts than non-smokers. With the exception of one non-smoker with very high adduct levels (52.8 adducts/10(8)), the control subjects showed the presence of barely detectable adducts in only 16% of the samples examined. The increased in vivo formation in some smokers and high variability of anti-BPDE-DNA adducts in coke oven workers suggests variations in genetically controlled activation/inactivation reactions of PAH metabolism.

Lung function was studied in 354 coke oven plant workers in the Lorraine collieries (Houilleres du Bassin de Lorraine, France) who retired between 1963 and 1982 The aim of this work was to study the long term effect of occupational exposure on lung function in retired coke oven workers from the HBL. This work is part of a study on mortality and morbidity in survivors.'7 It continues a previous study carried out in 1983 on mortality which showed an excess of mortality from lung cancer (standardised mortality ratio (SMR) = 2 51) with reference to the French male population.'8 Material and methodsThe study sample consisted of all the male workers from the two coke oven plants who had retired between 1 January 1963 and 31 December 1982 (536 subjects) and who were still alive on 1 January 1988 (354 subjects). They were born between 1902 and 1935. Executives were excluded from the study.The subjects were asked to attend a medical examination at the firm's occupational health centre. The protocol included a standard questionnaire, conducted by the occupational physician, concerning diseases treated or followed up for more than five years (cardiovascular, respiratory, digestive, infectious, and psychiatric diseases, traumas, cancers, etc), the questionnaire for the study of chronic bronchitis and pulmonary emphysema of the European Steel and Coal Commission (ECSC) of the EC,'9 and the notion of "regular overconsumption" of alcoholic drink. Because of low numbers we did not distinguish between smokers and ex-smokers. The respiratory symptoms taken into account were chronic bronchitis defined by a daily cough and phlegm for three consecutive months each year over a period of two years, wheezing or chest noises heard daily, day and night, and dyspnoea classified into five stages.To be aware of the respiratory symptoms in the period nearing retirement we sought information 316 on 12 May 2018 by guest. Protected by copyright.

The effect of past occupational exposure on morbidity was studied in 354 coke oven workers in Lorraine Collieries (France) who retired between 1963 and 1982, and were still alive in 1988; 96% of them participated in this study. Occupational exposure to respiratory hazards during the working life was retraced for each subject. No significant association between the occupational exposure and the frequency of ischemic cardiopathies, arterial hypertension, gastro-duodenal ulcers, and respiratory symptoms was revealed. However, subjects who had worked on the Ovens, in the Workshops, and in the Byproducts showed a prevalence of arterial hypertension significantly higher than the non- or slightly exposed subjects. The healthy worker effect phenomenon, the exclusion of deceased subjects, and the small size of this retiree population may conceal possible differences between exposure groups.

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