A dual assay for the specific screening of 3-methylcholanthrene- and phenobarbital-like chemical inducers of cytochrome P-450 monooxygenases |
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Authors: | P Lesca A Fournier P Lecointe T Cresteil |
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Institution: | a Laboratoire de Pharmacologie et de Toxicologie Fondamentales, 205 route de Narbonne, 31400, Toulouse, France b Laboratoire de Biochimie (INSERM U75), Faculté de Médecine Necker-Enfants malades, 156 rue de Vaugirard, 75730, Paris Cedex 15, France |
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Abstract: | We present and evaluate a dual assay, the CYPIA (Cytochrome P-450 induction assay) for the detection and the simultaneous identification of chemicals belonging either to the 3-methylcholanthrene or phenobarbital classes of cytochrome P-450 monooxygenase inducers. These inducers play an important role in the mutagenic activation of chemical compounds as well as in many pharmacological and toxicological events and therefore should be screened by drug and chemical designers. After treatment of male rats or mice by chemicals, the liver preparations (S9) have been used in the Salmonella typhimurium test, to activate either ethidium bromide or cyclophosphamide into mutagenic metabolites. These transformations are specifically catalyzed by cytochrome P-450-dependent monooxygenases induced by 3-methylcholanthrene-like and phenobarbital-like chemical inducers, respectively, The mutagenicity data were strikingly correlated with other methods (production of 3H]benzoa]pyrene bay-region metabolites, benzphetamine demethylase activity, immunological double-diffusion analysis). Compared to the latter methods, the CYPIA, based on a single and widespread technology, introduces an interesting simplification, and improves the specificity and the sensitivity of the responses. |
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Keywords: | CYPIA Cytochrome P-450 induction assay Aro Aroclor 1254 MC 3-methylcholanthrene PB phenobarbital EtBr ethidium bromide CPA cyclophosphamide BP P-450 cytochrome P-450 |
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