Possible role of DT-diaphorase in the bioactivation of antitumor quinones.
Menadione derivatives that are toxic to tumor cells are believed to be reduced intracellularly to species that react with DNA. In this communication, we report evidence that one of these derivatives, 3-bromomethylmenadione, is reduced by DT-diaphorases present in rat liver cytosol and in rat 9L brain tumor cells. Dicoumarol, an inhibitor of DT-diaphorases was found to inhibit both the reduction of 3-bromomethylmenadione and its mutagenicity to Salmonella typhimurium TA 97. Homogenates of rat 9L cells were found to contain relatively high levels of DT-diaphorase, suggesting that these tumor cells may be relatively sensitive to antitumor quinones that are activated by this enzyme.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D001728:Dicumarol / Q000494:pharmacology; D016660:NAD(P)H Dehydrogenase (Quinone); D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D011808:Quinone Reductases / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000378:metabolism; D024483:Vitamin K 3 / Q000031:analogs & derivatives*
D011809:Quinones; D014812:Vitamin K; C037393:3-bromomethylmenadione; D024483:Vitamin K 3; D001728:Dicumarol; D009247:NADH, NADPH Oxidoreductases; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases