Enhancement of DNA binding, mutagenicity and carcinogenicity of polycyclic aromatic hydrocarbons after induction of cytochrome P-450 by ellipticines in rats and mice.
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| Abstract |
Pretreatment of rats by ellipticines enhanced the microsomal concentration of cytochrome P-450, benzo[alpha]pyrene (BP) metabolism and activation and, a smaller extent, ethoxycoumarin deethylation, but not acetanilide hydroxylation. This increased BP biotransformation was essentially due to the formation of bay-region metabolites, BP 9,10-diol, BP 7,8-diol and 9-hydroxy-BP, or to the formation of BP 7,8-diol-9,10-epoxide- and of 9-hydroxy-BP 4,5-oxide-DNA adducts. In the ellipticine series, 9-fluoroellipticine (9-FE) presents a slight inducing potency compared with the parent and 9-hydroxy molecules. Pretreatment of mice with 9-hydroxyellipticine (9-OHE) led also to an increased mutagenicity of BP and to an augmentation of skin carcinogenesis by 7,12-dimethylbenz[alpha]anthracene (DMBA). These results clearly show that 9-OHE induces the biosynthesis of cytochrome P-450 which markedly stimulates the mutagenic and carcinogenic potentialities of polycyclic aromatic hydrocarbons (PAH).
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| Authors | T Cresteil, P Lesca |
| Journal | Chemico-biological interactions (Chem Biol Interact) Vol. 47 Issue 2 Pg. 145-56 (Nov 1983) ISSN: 0009-2797 [Print] Ireland |
| PMID | 6317209 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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