First Author | Radjendirane V | Year | 1998 |
Journal | J Biol Chem | Volume | 273 |
Issue | 13 | Pages | 7382-9 |
PubMed ID | 9516435 | Mgi Jnum | J:46669 |
Mgi Id | MGI:1201747 | Doi | 10.1074/jbc.273.13.7382 |
Citation | Radjendirane V, et al. (1998) Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity. J Biol Chem 273(13):7382-9 |
abstractText | 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. |