Aromatic DNA adduct levels in coke oven workers: correlation with polymorphisms in genes GSTP1, GSTM1, GSTT1 and CYP1A1.
The aim of this study was to use DNA adducts levels, detected by 32P-postlabelling, as a biomarker to assess human exposure to polycyclic aromatic hydrocarbons (PAHs) from a coke oven plant and explore the possible association between CYP1A1 MspI, GSTP1, GSTM1 and GSTT1 genotypes, and smoking status on bulky DNA adduct formation. A large amount of inter-individual variation in adduct level was observed among workers with the same job and the same smoking habits. No significant differences were observed in DNA adduct levels between the coke oven workers and control group. Smokers in the control group had significantly higher DNA adducts than the non-smokers in the same group (35.13+/-21.11 versus 11.18+/-8.00, per 10(8) nucleotides, P=0.003). In this group, the correlation between the level of DNA adducts and the cigarettes smoked was strongly significant (r=0.70, P<0.0005), but no correlation was found among the coke oven workers. Among non-smokers there was a significant difference between the control group and the coke oven workers (11.18+/-8.00 versus 24.62+/-15.20, per 10(8) nucleotides, P=0.03). These results suggests that tobacco smoke could behave as a confounding factor for evaluation of DNA adducts arising from occupational exposure. The levels of DNA adducts in smokers not occupationally exposed to PAHs is dependent on the polymorphisms CYP1A1 MspI in the 3' non-coding region (49.04+/-22.18 versus 25.85+/-15.87, per 10(8) nucleotides, P<0.05), but no effect was observed for the GST genotypes studied.
Teixeira
João Paulo
JP
Environmental Health and Toxicology Department, National Institute of Health, Largo 1 de Dezembro, 4000 Porto, Portugal.
Gaspar
Jorge
J
Martinho
Gabriela
G
Silva
Susana
S
Rodrigues
Sónia
S
Mayan
Olga
O
Martin
Elizabeth
E
Farmer
Peter B
PB
Rueff
José
J
D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D018736:DNA Adducts; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D016273:Occupational Exposure; D011110:Polymorphism, Genetic
D019363:Cytochrome P-450 CYP1A1; D018736:DNA Adducts; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human