8,9-Dihydroxy-8,9-dihydrodibenzo[ a , l ]pyrene is a potent morphological cell-transforming agent in C3H10T 1 / 2 Cl8 mouse embryo fibroblasts in the absence of detectable stable covalent DNA adducts

Open Access
Publisher Website
Google Scholar
Abstract
The comparative genotoxic effects of racemic trans -8,9-dihydroxy-8,9-dihydrodibenzo[ a , l ]pyrene ( trans- DB[ a , l ]P-8,9-diol), the metabolic K-region dihydrodiol of dibenzo[ a , l ] pyrene (DB[ a , l ]P) (dibenzo[ def , p ]chrysene) and DB[ a , l ]P in transformable mouse embryo C3H10T 1 / 2 Cl8 (C3H10T 1 / 2 ) fibroblasts was investigated. The C3H10T 1 / 2 mouse embryo morphological cell-transforming activities of these polycyclic aromatic hydrocarbons (PAHs) were assayed using concentration–response studies. At concentrations of 33 nM and above both trans- DB[ a , l ]P-8,9-diol and DB[ a , l ]P produced significant (and similar) numbers of type II and III foci per dish and numbers of dishes with type II and II foci. Concomitant cytotoxicity studies revealed a reduction in colony survival of ~25% up to 198 nM for both PAHs. DNA adducts of trans- DB[ a , l ]P-8,9-diol and DB[ a , l ]P in C3H10T 1 / 2 cells were analyzed by a 32 P-post-labeling TLC/HPLC method. No adducts were observed in the DNA of C3H10T 1 / 2 cells treated with trans- DB[ a , l ]P-8,9-diol at concentrations that induced morphological cell transformation. Under the same exposure and chromatographic conditions, DNA adducts of deoxyadenosine and deoxyguanosine derived from the fjord region anti -DB[ a , l ]P-11,12-diol-13,14-epoxide and syn- DB[ a , l ]P-11,12-diol-13,14-epoxide were observed in the DNA of DB[ a , l ]P-treated cells. These results indicate that trans- DB[ a , l ]P-8,9-diol has intrinsic genotoxic activity equal to that of DB[ a , l ]P, based on morphological cell transformation of mouse embryo fibroblasts. The activity of trans- DB[ a , l ]P-8,9-diol is apparently not associated with the formation of observable stable covalent DNA adducts. These results suggest that under appropriate conditions, trans- DB[ a , l ]P-8,9-diol may serve as an intermediate in the genotoxicity of DB[ a , l ]P.

This publication has 28 references indexed in Scilit: