NAD(P)H : quinone oxidoreductase 1 deficiency increases susceptibility to benzo(a)pyrene-induced mouse skin carcinogenesis

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoprotein that catalyzes th e metabolic detoxification of quinones and their derivatives. This protects cells against quinone-induced oxidative stress, cytotoxicity, and mutageni city, C57BL6 NQO1-/- mice, deficient in NQO1 RNA and protein, were generate d in our laboratory, To investigate the role of NQO1 in chemical carcinogen esis, the dorsal skin of NQO1-deficient (NQO1-/-) and wild-type (NQO1+/+) m ice were treated with a single dose of benzo(a)pyrene, followed by twice we ekly applications of phorbol-12-myristate-13-acletate. The NQO1-/- mice sho wed a much higher frequency of skin tumor development when compared with th eir 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 result s demonstrate that NQO1 acts as an endogenous factor in protection against benzo(a)pyrene carcinogenicity.