title: Metabolic activation of dimethylnitrosamine to mutagens: role of cytochromes P-450 and P-448.
abstract: Pretreatment of hamsters with phenobarbitone, 3-methylcholanthrene and Arochlor 1254 induced the hepatic microsomal mixed function oxidases, yet decrease the efficiency of activation of dimethylnitrosamine (DMN) to intermediates mutagenic to the Salmonella typhimurium strain TA-100. Furthermore, no correlation was obtained between cytochrome P-450 content, microsomal demethylation of DMN and its activation to mutagens. These results indicate that the demethylation of DMN by the mixed-function oxidases is not the rate-limiting step in the metabolic activation of the carcinogen to mutagen(s), and that other microsomal or soluble enzymes may be involved.
mesh_terms: D000818:Animals; D001711:Biotransformation; D006224:Cricetinae; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics
chemical_list: D003580:Cytochromes; D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D004128:Dimethylnitrosamine