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8,9-DIHYDROXY-8,9-DIHYDRODIBENZO[A,L]PYRENE IS A POTENT MORPHOLOGICAL CELL-TRANSFORMING AGENT IN C3H10T1/2C18 MOUSE EMBRYO FIBROBLASTS IN THE ABSENCE OF DETECTABLE STABLE COVALENT DNA ADDUCTS
Citation:
Nesnow, S, C. R. Davis, W. T. Padgett, L D. Adams, M. Yacopucci, AND L C. King. 8,9-DIHYDROXY-8,9-DIHYDRODIBENZO[A,L]PYRENE IS A POTENT MORPHOLOGICAL CELL-TRANSFORMING AGENT IN C3H10T1/2C18 MOUSE EMBRYO FIBROBLASTS IN THE ABSENCE OF DETECTABLE STABLE COVALENT DNA ADDUCTS. CARCINOGENESIS 21(6):1253-1257, (2000).
Description:
The comparative genotoxic effects of racemic trans-8,9dihydroxy-8,9-dihydrodibenzo[a,l]pyrene (trans- DB[a,l]P8,9-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 C3HIOT1/2C18 (C3HIOT1/2) fibroblasts was investigated. The C3HIOT1/2, 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 C3H1OT1/2 cells were analyzed by a 32P-postlabeling TLC/HPLC method. No adducts were observed in the DNA of C3HIOT1/2 cells treated with trans-DB[a,l]P8,9-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 antiDB[a,I]P-11,12-diol-13,14-epoxide and syn-DB[a,l]P-11,12diol-13,14-epoxide were observed in the DNA of DB[a,l]P-treated cells. These results indicate that trans-DB[a,l]P-8,9diol 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,1]P-8,9-diol may serve as an intermediate in the genotoxicity of DB[a,l]P.