NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms.
NAD(P)H:quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase that is involved in chemoprotection and can also bioactivate certain antitumor quinones. This review focuses on detoxification reactions catalyzed by NQO1 and its role in antioxidant defense via the generation of antioxidant forms of ubiquinone and vitamin E. Bioactivation reactions catalyzed by NQO1 are also summarized and the development of new antitumor agents for the therapy of solid tumors with marked NQO1 content is reviewed. NQO1 gene regulation and the role of the antioxidant response element and the xenobiotic response element in transcriptional regulation is summarized. An overview of genetic polymorphisms in NQO1 is presented and biological significance for chemoprotection, cancer susceptibility and antitumor drug action is discussed.
Ross
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D
Department of Pharmaceutical Sciences, School of Pharmacy and Cancer Center, Box C-238, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA. david.ross@uchsc.edu
Kepa
J K
JK
Winski
S L
SL
Beall
H D
HD
Anwar
A
A
Siegel
D
D
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics; D001711:Biotransformation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008658:Inactivation, Metabolic; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic
D018906:Antineoplastic Agents, Alkylating; D016660:NAD(P)H Dehydrogenase (Quinone)