Polycyclic aromatic hydrocarbon-DNA adducts in smokers and their relationship to micronutrient levels and the glutathione-s-transferase m1 genotype

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 β-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, β-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, β-carotene and vitamin C in modulating adduct formation and lung cancer risk.