Journal Article

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

Stephen Nesnow, Christine Davis, William T. Padgett, Linda Adams, Michele Yacopucci and Leon C. King

in Carcinogenesis

Volume 21, issue 6, pages 1253-1257
Published in print June 2000 | ISSN: 0143-3334
Published online June 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.6.1253
8,9-Dihydroxy-8,9-dihydrodibenzo[a,l]pyrene is a potent morphological cell-transforming agent in C3H10T1/2Cl8 mouse embryo fibroblasts in the absence of detectable stable covalent DNA adducts

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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 C3H10T1/2Cl8 (C3H10T1/2) fibroblasts was investigated. The C3H10T1/2 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 C3H10T1/2 cells were analyzed by a 32P-post-labeling TLC/HPLC method. No adducts were observed in the DNA of C3H10T1/2 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.

Keywords: B[a]P, benzo[a]pyrene; C3H10T1/2, C3H10T1/2Cl8; CT-DNA, calf thymus DNA; DB[a,l]P, dibenzo[a,l]pyrene; trans-DB[a,l]P-8,9-diol, (±)-trans-8,9-dihydroxy-8,9-dihydroDB[a,l]P; anti-DB[a,l]PDE, anti-DB[a,l]P-11,12-diol-13,14-epoxide; syn-DB[a,l]PDE, syn-DB[a,l]P-11,12-diol-13,14-epoxide; PAHs, polycyclic aromatic hydrocarbons; PEI, polyethyleneimine.

Journal Article.  3924 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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