Studies on the metabolism of dimethylnitrosamine in vitro by rat-liver preparations. I. Comparison with mixed-function oxidase enzymes.
1. The metabolism of dimethylnitrosamine (DMN) to formaldehyde by rat-liver preparations has been studied at substrate concn. of 0.5, 5 and 50 mM and compared with mixed-function oxidase enzyme activities. 2. The microsomal metabolism of low (0.5 and 5 mM) and high (50 mM) substrate concn. of DMN was differentially affected by acetone addition or KI treatment. 3. A series of heterocyclic compounds related to pyrazole were potent inhibitors of metabolism of 0.5 and 5 mM DMN at concn. which had little effect on mixed-function oxidase activities. In contrast, purine addition slightly stimulated the metabolism of low but not high concn. of DMN. 4. The results are consistent with the suggestion that multiple enzymic pathway(s) are involved in hepatic DMN metabolism and that some of these pathway(s) may be independent of cytochrome P-450.
D000096:Acetone / Q000494:pharmacology; D000818:Animals; D004128:Dimethylnitrosamine / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D011193:Potassium Iodide / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D011720:Pyrazoles; D000096:Acetone; D011193:Potassium Iodide; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D004851:Epoxide Hydrolases; D004128:Dimethylnitrosamine