First Author | Long DJ 2nd | Year | 2000 |
Journal | Cancer Res | Volume | 60 |
Issue | 21 | Pages | 5913-5 |
PubMed ID | 11085502 | Mgi Jnum | J:66196 |
Mgi Id | MGI:1928117 | Citation | Long DJ 2nd, et al. (2000) NAD(P)H:quinone oxidoreductase 1 deficiency increases susceptibility to benzo(a)pyrene-induced mouse skin carcinogenesis. Cancer Res 60(21):5913-5 |
abstractText | NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoprotein that catalyzes the metabolic detoxification of quinones and their derivatives. This protects cells against quinone-induced oxidative stress, cytotoxicity, and mutagenicity. C57BL6 NQO1-/- mice, deficient in NQO1 RNA and protein, were generated in our laboratory. To investigate the role of NQO1 in chemical carcinogenesis, the dorsal skin of NQO1-deficient (NQO1-/-) and wild-type (NQO1+/+) mice were treated with a single dose of benzo(a)pyrene, followed by twice weekly applications of phorbol-12-myristate-13-acetate. The NQO1-/- mice showed a much higher frequency of skin tumor development when compared with their wild-type littermates. Interestingly, the male NQO1-/- mice were slower to develop skin tumors than their NQO1-/- female littermates. Histological analysis of the NQO1-/- tumors showed proliferative activity. These results demonstrate that NQO1 acts as an endogenous factor in protection against benzo(a)pyrene carcinogenicity. |