Role of DT diaphorase the cytotoxicity of menadione and 4-nitroquinoline-1-oxide in cultured mammalian fibroblastic cells.
The role of DT diaphorase on the cytotoxicity (reduction in colony formation frequency) of menadione and 4-nitroquinoline-1-oxide (4NQO) was examined in two fibroblastic cell lines (Chinese hamster V79H3 cells and NG2 Syrian hamster cells). The addition of dicoumarol (10(-4) M-3 x 10(-4) M), a specific inhibitor of DT diaphorase, resulted in an intensification of the cytotoxicity of menadione, supporting the hypothesis that DT diaphorase protects cells against the oxidative stress induced by quinones. On the other hand, the toxicity of 4NQO was greatly reduced by the addition of dicoumarol (10(-5) M-3 x 10(-4) M), showing that DT diaphorase is the key (or the sole) enzyme involved in the activation of 4NQO in the above cells.
Life Science Research Laboratory, Japan Tobacco Inc., Kanagawa.
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Tsuda
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D001728:Dicumarol / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D008099:Liver / Q000166:cytology / Q000201:enzymology; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases / Q000502:physiology*; D051381:Rats; D014812:Vitamin K / Q000633:toxicity*
D014812:Vitamin K; D015112:4-Nitroquinoline-1-oxide; D001728:Dicumarol; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases