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 polycyclic 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 beta-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, beta-carotene, vitamin C and vitamin E. Since genetic deficiency in the detoxifying enzyme glutathione S-transferase 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/10(8) nucleotides (range 1.00-24.1/10(8)). 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 < or = 0.05) and with smoking-adjusted vitamin C serum levels (r = -0.22, P < or = 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, P < or = 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 = -0.35, P < or = 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, beta-carotene and vitamin C in modulating adduct formation and lung cancer risk.
Grinberg-Funes
R A
RA
Hoffman-La Roche, Nutley, NJ 07110.
Singh
V N
VN
Perera
F P
FP
Bell
D A
DA
Young
T L
TL
Dickey
C
C
Wang
L W
LW
Santella
R M
RM
D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000097:blood; D018736:DNA Adducts / Q000032:analysis*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011083:Polycyclic Compounds / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D014801:Vitamin A / Q000008:administration & dosage / Q000097:blood; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood; D014815:Vitamins / Q000097:blood*
D018736:DNA Adducts; D007527:Isoenzymes; D011083:Polycyclic Compounds; D014815:Vitamins; D014801:Vitamin A; D014810:Vitamin E; D005982:Glutathione Transferase; D001205:Ascorbic Acid