The role of highly purified forms of rat liver cytochrome P-450 in the dimethylation of dimethylnitrosamine and its activation to mutagens.
Highly purified NADPH-cytochrome P-450 reductase and the major phenobarbital (PB) and beta-naphthoflavone (beta NF) forms of cytochrome P-450 were used in reconstituted systems to study the demethylation and subsequent activation of dimethylnitrosamine (DMN) to mutagenic intermediates. Both forms of cytochrome P-450 were active in the demethylation of DMN, cytochrome P-450 from PB-treated animals being more efficient, generating nearly twice as much formaldehyde per nmol of haemoprotein. Neither form of the cytochrome could activate DMN to mutagens in the Ames test. These findings indicate that DMN demethylation does not lead to its activation to mutagenic products.
D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism* / Q000633:toxicity; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009153:Mutagens; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D004128:Dimethylnitrosamine; D010634:Phenobarbital