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

The comparative genotoxic effects of racemic trans-8,9-dihydroxy-8,9-dihydr odibenzo[a,l]pyrene (trans-DB[a,l]P-8,9-diol), the metabolic K-region dihyd rodiol of dibenzo[a,l] pyrene (DB[a,l]P) (dibenzo[def,p]chrysene) and DB[a, l]P in transformable mouse embryo C3H10T1/2C18 (C3H10T1/2) fibroblasts was investigated. The C3H10T1/2 mouse embryo morphological cell-transforming ac tivities of these polycyclic aromatic hydrocarbons (PAHs) were assayed usin g 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) nu mbers of type II and III foci per dish and numbers of dishes with type II a nd II foci, Concomitant cytotoxicity studies revealed a reduction in colony survival of similar to 25% up to 198 nM for both PAHs, DNA adducts of tran s-DB[a,l]P-8,9-diol and DB[a,l]P in C3H10T1/2 cells were analyzed by a P-32 -post-labeling TLC/HPLC method. No adducts were observed in the DNA of C3H1 0T1/2 cells treated with trans-DB[a,l]P-8,9-diol at concentrations that ind uced morphological cell transformation, Under the same exposure and chromat ographic conditions, DNA adducts of deoxyadenosine and deoxyguanosine deriv ed 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 g enotoxic activity equal to that of DB[a,l]P, based on morphological cell tr ansformation 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 conditi ons, trans-DB[a,l]P-8,9-diol may serve as an intermediate in the genotoxici ty of DB[a,l]P.