title: Involvement of lauric acid hydroxylase in the activation of beta-substituted nitrosamines.
abstract: The mutagenicity of N-nitrosobis (2-hydroxypropyl) amine (BHP), N-nitrosobis(2-oxopropyl)amine (BOP) and N-nitroso-(2-hydroxy-propyl) (2-oxopropyl) amine (HPOP) was measured in V79 cells. Hepatocytes, used to metabolize (activate) the nitrosamines, were isolated from untreated Syrian hamsters (control) and hamsters treated with clofibrate (CLO) or dehydroepiandrosterone (DHEA) in vivo. BHP and HPOP mutagenicity increased 3- and 2-fold when hepatocytes from CLO- and DHEA-treated hamsters were used. BOP mutagenicity did not increase. 10-Undecynoic acid, a lauric acid hydroxylase inhibitor, inhibited the increase in BHP and HPOP mutagenicity by 80-90% but did not affect that of BOP. Antimycin A1, a fatty acyl coenzyme A beta-oxidase inhibitor did not affect the mutagenicity of these nitrosamines. Lauric acid hydroxylase, probably omega-1 hydroxylase (cytochrome P-450 IVA2), appears to be involved in the activation of BHP and HPOP.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68105-1065.
authors.forename: T A
authors.initials: TA
authors.lastname: Lawson
mesh_terms: D042962:Acyl-CoA Oxidase; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D009602:Nitrosamines / Q000378:metabolism / Q000494:pharmacology*; D010088:Oxidoreductases / Q000378:metabolism
chemical_list: D002273:Carcinogens; D009153:Mutagens; D009602:Nitrosamines; C012457:diisopropanolnitrosamine; C013622:nitrosobis(2-oxopropyl)amine; C013624:N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D042926:Cytochrome P-450 CYP4A; D042962:Acyl-CoA Oxidase