© 1994 Oxford University Press
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Polycyclic aromatic hydrocarbon–DNA adducts in smokers and their relationship to micronutrient levels and the glutathione-S-transferase M1 genotype
Hoffman-La Roche, Nutley, NJ 07110
1Columbia Presbyterian Cancer Center and Columbia School of Public Health New York, NY 10032
2National Institute of Environmental Health Science Research Triangle Park, NC 27709, USA
3To whom reprint requests should be sent at the Division of Environmental Sciences, 701 West 168th Street, Room 505, New York, NY 10032, USA
Sixty-three male cigarette smokers were entered into a cross-sectional study to determine whether inverse associations existed between polycydlic aromatic hydrocarbon (PAH)—DNA adduct levels and intake/serum levels of vitamin A, vitamin C and vitamin E. Associations between PAH–DNA adducts and intakes of carotene, as well as serum levels of ß-carotene, were also determined. Fasting blood samples were collected for assays of PAH—DNA adducts in circulating mononuclear cells, plasma cotinine and serum levels of vitamin A, ß-carotene, vitamin C and vitamin E. Since genetic deficiency in the detoxifying enzyme glutathione S-traasferase M1 (GSTM1) has been associated with increased risk of lung cancer, GSTM1 genotype was also determined. Analysis of PAH—DNA adducts by competitive enzyme-linked immunosorbent assay (ELISA) indicated that 70% of the subjects had detectable adducts, with a mean of 4.38 adducts/108 nucleotides (range 1.00–24.1/108 Pearson's method was utilized to determine whether any associations existed between the various host variables and PAH—DNA adducts. Previously, no significant associations were found between PAH—DNA adducts and cigarettes smoked/day, pack-years, daily/life time tar exposures or plasma cotinine levels (Santella et al., Carcinogenesis, 13, 2041–2045, 1992). PAH—DNA adducts were inversely associated with serum cholesterol-adjusted vitamin E levels (r = –0.25, P 
0.05) and with smoking-adjusted vitamin C serum levels (r = –0.22, 0.09). Stratification by GSTM1 genotype indicated that these associations were limited to subjects with the null genotype. The relationship between adducts and serum cholesterol-adjusted vitamin E was significant in those of the null genotype (r = –0.38, 0.04), but not in those with the gene present (r = –0.12, P = 0.5). Similarly, for smoking-adjusted vitamin C, the relationship with adducts was stronger in subjects with the null genotype (r = –035, P .0.06) than in those with GSTM1 present (r = –0.05, P = 0.77). These results are consistent with findings of prior epidemiological studies Identifying significant inverse associations between anti-oxidant micronutrient status or GSTM1 genotype and the incidence of lung cancer. Additional studies should be conducted to confirm a possible role for vitamin E in PAH—DNA adduct formation and to explore further the possible roles of vitamin A, ß-carotene and vitamin C in modulating adduct formation and lung cancer risk.
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