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.

Objectives-To investigate possible relations between respiratory health and past airborne exposure to refractory ceramic fibres (RCFs) and respirable dust in workers at six European factories, studied previously in 1987. Methods-The target population comprised all current workers associated with RCF production, plus others who had participated in 1987 "leavers". Information was collected on personal characteristics, chest radiographs, lung function, respiratory symptoms, smoking, and full occupational history. Regression analysis was used to study relations between indices of health of individual workers and of cumulative exposure to airborne dust and fibres, and likely past exposure to asbestos. Results and discussion-774 workers participated (90% of current workers, 37% of leavers). Profusion of small opacities in exposed workers (51% 0/1+; 8% 1/0+) was similar to that among an unexposed control group but higher than in new readings of the 1987 study films (11% 0/1+, 2% 1/0+). The large diVerence between 1987 and recent films may be, at least in part, a reading artefact associated with film appearance. Small opacities of International Labour Organisation (ILO) category 1/0+ were not associated with exposure. An association of borderline significance overall between 0/1+ opacities and exposure to respirable fibres was found for some exposure periods only, the time related pattern being biologically implausible. Pleural changes were related to age and exposure to asbestos, and findings were consistent with an eVect of time since first exposure to RCFs. Among men, forced expired volume in 1 second (FEV 1 ) and forced vital capacity (FVC) were inversely related to exposure to fibres, in current smokers only. FEV 1 / FVC ratio and transfer factor (TL CO ) were not related to exposures. The estimated restrictive eVect was on average mild. Prevalence of respiratory symptoms was low. Chronic bronchitis and its associated symptoms (cough, phlegm) showed some association with recent exposure to respirable fibres. This could be due to an irritant eVect of RCFs. (Occup Environ Med 2001;58:800-810)

Objective-To investigate if blood Cu++/Zn++ superoxide dismutase, glutathione peroxidase, catalase, and total plasma antioxidant activities could be markers of biological activity resulting from exposure to respirable coal mine dust in active miners, and of pneumoconiosis in retired miners. Methods-Blood samples were randomly obtained from active surface workers (n = 30) and underground miners (n = 34), and from retired miners without (n = 21), and with (n = 33) pneumoconiosis. Antioxidant enzyme activities and total plasma antioxidants were measured in erythrocytes and plasma. Non-parametric tests were completed by analyses of covariance to compare antioxidants between groups, taking into account potential confounding factors (age, smoking history (pack-years)).Results-Erythrocyte Cu++IZn++ superoxide dismutase activity was significantly higher in the group of underground miners than the group of surface workers. The differences in total plasma antioxidants and plasma glutathione peroxidase activity between both groups were related to age. Glutathione peroxidase activity increased in the plasma of retired miners with pneumoconiosis, compared with retired miners without pneumoconiosis. No differences were found either in erythrocyte antioxidant enzyme activities or in total plasma antioxidants between the groups of retired miners without and with pneumoconiosis. Conclusions-In this study, erythrocyte Cu++/Zn++ superoxide dismutase activity may be considered as a marker of effect of respirable coal mine dust in exposed workers. This result is in agreement with the hypothesis that reactive oxygen species are involved in cell injury induced by coal mine dust, and may be predictive of the degree ofinflammation and pneumoconiosis induced by coal mine dust. The increase in glutathione peroxidase activity in the plasma of retired miners with pneumoconiosis may be the result of a response to the increasing hydrogen peroxide (HO,) production due to the disease process.(Occup Environ Med 1996;53:41-45)

Objectives-To assess the effect of an occupational exposure to talc dust on respiratory health. The prevalence of dyspnoea also increased after adjustment for smoking categories and age in a logistic regression. The prevalence of small radiological opacities was significantly related to age and to the exposure after adjustment for age and smoking categories. The incidence of new opacities between the two radiographs (11 new opacities with a profusion higher than 01) was significantly related to smoking (10 out of 11 are smokers) but not to the exposure. Conclusion-This study shows an effect of high levels of talc dust both on functional variables and on the prevalence of small radiological images, but provides no clear evidence about the possible effect of present levels of exposure.