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Radjendirane V , Joseph P , Lee YH , Kimura S , Klein-Szanto AJP , Gonzalez FJ , Jaiswal AK
Disruption of the DT diaphorase (NQ01) gene in mice leads to increased menadione toxicity
Journal of Biological Chemistry. 1998 Mar 27;273(13) :7382-7389
PMID: ISI:000072738500031   
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NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme that catalyzes two-electron reductive metabolism and detoxification of quinones and their derivatives leading to protection of cells against redox cycling and oxidative stress. To examine the in vivo role of NQO1, a NQO1-null mouse was produced using targeted gene disruption. Mice lacking NQO1 gene expression showed no detectable phenotype and were indistinguishable from wild-type mice. However, NQO1-null mice exhibited increased toxicity when administered menadione compared with wild-type mice. These results establish a role for NQO1 in protection against quinone toxicity. The NQO1-null mice are a model for NQO1 deficiency in humans and can be used to determine the role of this enzyme in sensitivity to toxicity and carcinogenesis.
Times Cited: 40 English Article ZD917 J BIOL CHEM