Characterization of naphtho[1,2-a]pyrene and naphtho[1,2-e]pyrene DNA adducts in C3H10T1/2 fibroblasts

Abstract Polycyclic aromatic hydrocarbons (PAHs) are a class of carcinogenic chemicals that are ubiquitous in the environment. Fjord-region naphthopyrene isomers are structurally similar to the potent fjord-region PAH carcinogen dibenzo[ a , l ]pyrene and thus have the potential to be potent carcinogens. Naphtho[1,2- a ]pyrene (N[1,2- a ]P) exhibited similar bacterial mutagenicity and morphological cell transforming activity when compared to benzo[ a ]pyrene (B[ a ]P), whereas the structural isomer, naphtho[1,2- e ]pyrene (N[1,2- e ]P) was inactive is these bioassays. In this study, we examined the formation of DNA adducts in C3H10T1/2Cl8 (C3H10T1/2) mouse embryo fibroblasts exposed to N[1,2- a ]P or N[1,2- e ]P and their respective dihydrodiols. The DNA adducts were characterized by co-chromatography with reaction products from anti -N[1,2- a ]P diol epoxide (DE) or anti -N[1,2- e ]PDE and polydeoxyadenosine (dAdo) or oligodeoxyguanosine (dGuo). C3H10T1/2 fibroblasts exposed to N[1,2- a ]P or N[1,2- a ]P-9,10-diol produced both anti -N[1,2- a ]P-DE-dAdo and -dGuo adducts with total DNA adduction levels of 22.2 to 33.3 pmol DNA adducts/μg DNA. C3H10T1/2 fibroblasts exposed to N[1,2- e ]P produced 2 major and 1 minor adducts. C3H10T1/2 fibroblasts exposed to N[1,2- e ]P-11,12-diol produced 2 major adducts. All of the identified adducts were anti -N[1,2- e ]PDE-dGuo and -dAdo adducts. While the total DNA adduct level in N[1,2- e ]P-11,12-diol-treated fibroblasts was extremely high, 105.9 pmol DNA adducts/μg DNA, the level in N[1,2- e ]P-treated fibroblasts was 1.47 pmol DNA adducts/μg DNA. We conclude that lack of biological activity of N[1,2- e ]P may be related to its inability to form sufficient amounts of N[1,2- e ]P-11,12-diol, which would then be metabolized to sufficient amounts of anti -N[1,2- e ]PDE needed to transform these fibroblasts.