Polycyclic aromatic hydrocarbons (PAH) are formed due to incomplete combustion of fossil fuels and are ubiquitously present in the environment. Benzo [a]pyrene (B[a]P) is one of a large number of PAH and is frequently used as a representative indicator of total PAH exposure (1). B[a]P is usually inhaled and deposited in the lower lung, where it is readily absorbed. It is then metabolically activated by cytochrome P450 to highly reactive electrophilic forms, including phenol, trans-dihydrodiols, arene oxides, and diol-epoxides, which may be responsible for most of its observed cytotoxic, mutagenic, and carcinogenic effects (1, 2). Biotransformation of chemicals involves metabolic activation and detoxification pathways, which are known to play a primary role in chemical carcinogenesis (3).Polymorphisms in the genes for metabolism are largely responsible for the different abilities of individuals to activate and detoxify genotoxic agents. Glutathione S-transferase (GS T), which forms a multigene family of phase II detoxification enzyme, is involved in the metabolic detoxification of PAH (4-6). This enzyme plays an important role in protecting DNA against damage and adduct formation, by glutathione conjugation to electrophilic substances, particularly those with lipophilic compounds (7). The polymorphism of GSTM1 and GSTT1 gene loci is caused by a gene deletion, which causes a virtual absence of enzyme activity in individuals with the GSTM1-and GSTT1-null genotypes. The GSTM1-null genotype has been known to be associated with an increased risk for various environmentally-induced cancers (8, 9) and similarly, the GSTT1-null genotype with an increased risk for primary brain tumors and myelodysplastic syndromes (10). However, the genotoxic effect of GSTT1 polymorphism is not well understood compared to that of the GSTM1 polymorphism (4, 11). The coordinated activities of polymorphisms of GST may influence cytotoxic, mutagenic, and carcinogenic effects (5, 12). Epidemiologic studies indicate that the coordinated activities of polymorphisms in the GSTM1 and GSTT1 genes are associated with an increased risk for lung and bladder cancers (13,14).Although the associations between polymorphisms in genes for metabolism and cancer development has been known, the exact mechanisms of the relationships have not been elucidated. Little has been published on the relationship between these PAH-metabolizing enzymes and the formation of DNA adducts, which reflect DNA damage as a result of environmental exposures to PAH (15). In particular, there are no published data on the relationship between the GSTM1 and GSTT1 polymorphisms and DNA-protein crosslinks (DPC) formation resulting from exposure to B[a]P. DPC is known to be produced by oxygen radicals and other reactive species (16). Exposures to ionizing radiation, formaldehyde, and hexavalent chromium are also known to result in the induction of We investigated the influence of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) polymorphisms upon DNA-protein...
