title: Influence of DT diaphorase on the mutagenicity of organic and inorganic compounds.
abstract: The metabolic activation or detoxification of mutagens and carcinogens of several chemical classes was investigated in the presence of various rat liver and lung subcellular fractions and of dicoumarol, a specific inhibitor of DT diaphorase activity. His- Salmonella typhimurium strains were used as targets of mutagenicity. Dicoumarol partially prevented the metabolic activation of some promutagens, such as the heterocyclic amines 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and 3-amino-1-methyl-5H-pyrido[4,3-b]indole, and a cigarette smoke condensate. Moreover, detailed experiments, also using purified enzyme, confirmed the participation of DT diaphorase in the metabolic reduction of 4-nitroquinoline N-oxide 4NQO and of hexavalent chromium [Cr(VI)] compounds. The results obtained provide evidence for broad involvement of DT diaphorase in the metabolism of both organic and inorganic mutagens and carcinogens. Moreover, they suggest a dual role of this enzyme, providing not only a cellular detoxifying system but also, with a few substrates, an activating mechanism.
mesh_terms: D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism; D001728:Dicumarol / Q000494:pharmacology; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D011808:Quinone Reductases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects*
chemical_list: D009153:Mutagens; D001728:Dicumarol; D011808:Quinone Reductases