Polymorphisms of the GSTP1 and GSTM1 genes and PAH-DNA adducts in human mononuclear white blood cells

Glutathione S-transferases (GSTs) are an important port of the protection s ystem against a wide range of potentially harmful chemical compounds. GSTP1 and GSTM1 are mainly involved in detoxification reactions of PAH carcinoge nic intermediates produced by cytochrome P450 (CYP). Polymorphism of the GS T genes may influence the level of carcinogen-DNA adducts in human tissues and be associated with individual susceptibility to carcinogens. in this st udy, we examined the effect of common polymorphism in exon 5 (105Ile --> Va l) of the GSTP1 gene, alone and in combination with GSTM1-deletion polymorp hism, on the level of PAH-DNA adducts measured by P-32-postlabeling assay i n mononuclear white blood cells collected in winter and in summer from a to tal of 170 healthy volunteers. When GSTP1 genotypes alone were compared, no statistically significant differences in adduct levels were found. However , smokers with GSTM1(null)/GSTP1-AG or -GG combined genotype showed signifi cantly higher adduct levels in summer than carriers of other GSTM1/GSTP1 co mbinations (5.60 +/- 5.10 vs. 3.45 +/- 4.28/108 nucleotides, P = 0.015). Am ong smokers carrying GSTP1-AG or -GG genotype, individuals with GSTM1(null) genotype had a significantly higher level of adducts in summer than subjec ts with GSTM1(+) genotype (5.60 +/- 5.10 vs. 1.82 +/- 1.98/10(8), P = 0.002 ) and GSTM1(null)/GSTP1-AA genotype carriers (5.60 +/- 5.10 vs. 4.13 +/- 5. 84/10(8), P = 0.03). When adduct levels measured either in winter or in the nonsmoker group were considered, no influence of GSTM1/GSTP1 genotypes was found. Our data show that the combined GSTM1 and GSTP1 genetic polymorphis ms may modulate PAH-DNA adduct levels in mononuclear WBCs from individuals exposed to specific carcinogenic compounds, e.g., tobacco smoke, in relativ ely lower-exposure environmental conditions (i.e., in summer). Environ. Mel . Mutagen. (C) 2000 Wiley-Liss, inc.