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© 1985 Oxford University Press

research-article

Activation and Inactivation of a Variety of Mutagenic Compounds by the Reconstituted System Containing Highly Purified Preparations of Cytochrome P-450 from Rat Liver

SUMIE KAWANO*,1, TETSUYA KAMATAKI{dagger}, KAORI MAEDA{ddagger}, RYUICHI KATO{dagger}, TOSHIKO NAKAO* and ISAO MIZOGUCHI*

*Tokyo Metropolitan Research Laboratory of Public Health Hyakunincho 3-24-1, Shinjuku-ku, Tokyo 160 {dagger}Department of Pharmacology, School of Medicine, Keio University Shinanomachi 35, Shinjuku-ku, Tokyo 160 {ddagger}Department of Pharmaceutics, Hoshi University Ebara 2-4-41, Shinagawa-ku, Tokyo 142, Japan

Activation and Inactivation of a Variety of Mutagenic Compounds by the Reconstituted System Containing Highly Purified Preparations of Cytochrome P-450 from Rat Liver. KAWANO, S., KAMATAKI, T., MAEDA, K., KATO, R., NAKAO, T., AND MIZOGUCHI, I. (1985). Fundam. Appl. Toxicol. 5, 487–498. Six cytochrome P-450 preparations from phenobarbital (PB)-treated rats and two preparations from ß-naphthoflavone (BNF)-treated rats were purified. Using Salmonella typhimurium TA98 the ability of these cytochrome P-450 preparations to mutagenically activate and inactivate a variety of carcinogens was examined. High- and low- spin forms of cytochrome P-448 isolated from BNF-treated rats (BNF-IIa and IId) activated various carcinogens. Both forms activated 2-aminofluorene, benzo[a]pyrene, and dibenz[a,c]anthracene. However, o-aminoazotoluene and 2-nitrofluorene were activated only by the low-spin form, and aflatoxin B1 only by the high-spin form. In contrast, only limited carcinogens were activated by some preparations from PB-treated rats. 2-Aminofluorene was activated by four PB-inducible preparations (PB-Ia, Ic, Id, and IIa), but only moderately. Unexpectedly, however, the most prominent activation of benzo[a]pyrene was observed with one preparation (PB-Id) from PB-treated rats. Direct mutagens to the S. typhimurium, 4-NQO and AF-2, were markedly inactivated by NADPH-cytochrome c (P-450) reductase without cytochrome P-450, One PB-inducible form (PB-Ic) inactivted 2-nitrofluorene, and the high- spin form of P-448 (BNF-IIa) inactivated AF-2


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