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

Activation and Inactivation of a Variety of Mutagenic Compoundsby the Reconstituted System Containing Highly Purified Preparationsof 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 preparationsfrom phenobarbital (PB)-treated rats and two preparations fromß-naphthoflavone (BNF)-treated rats were purified.Using Salmonella typhimurium TA98 the ability of these cytochromeP-450 preparations to mutagenically activate and inactivatea variety of carcinogens was examined. High- and low- spin formsof cytochrome P-448 isolated from BNF-treated rats (BNF-IIaand IId) activated various carcinogens. Both forms activated2-aminofluorene, benzo[a]pyrene, and dibenz[a,c]anthracene.However, o-aminoazotoluene and 2-nitrofluorene were activatedonly by the low-spin form, and aflatoxin B1 only by the high-spinform. In contrast, only limited carcinogens were activated bysome preparations from PB-treated rats. 2-Aminofluorene wasactivated by four PB-inducible preparations (PB-Ia, Ic, Id,and IIa), but only moderately. Unexpectedly, however, the mostprominent activation of benzo[a]pyrene was observed with onepreparation (PB-Id) from PB-treated rats. Direct mutagens tothe S. typhimurium, 4-NQO and AF-2, were markedly inactivatedby NADPH-cytochrome c (P-450) reductase without cytochrome P-450,One PB-inducible form (PB-Ic) inactivted 2-nitrofluorene, andthe high- spin form of P-448 (BNF-IIa) inactivated AF-2