Activation and inactivation of a variety of mutagenic compounds by the reconstituted system containing highly purified preparations of cytochrome P-450 from rat liver.
Six cytochrome P-450 preparations from phenobarbital (PB)-treated rats and two preparations from beta-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) inactivated 2-nitrofluorene, and the high-spin form of P-448 (BNF-IIa) inactivated AF-2.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds / Q000378:metabolism; D001571:Benzoflavones / Q000494:pharmacology; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D008099:Liver / Q000201:enzymology*; D008297:Male; D009153:Mutagens / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009574:Nitro Compounds / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
D000348:Aflatoxins; D000596:Amino Acids; D001391:Azo Compounds; D001571:Benzoflavones; D002273:Carcinogens; D009153:Mutagens; D009574:Nitro Compounds; D011083:Polycyclic Compounds; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D009251:NADPH-Ferrihemoprotein Reductase; D010634:Phenobarbital