NAD(P)H:quinone oxidoreductase 1 (NQO1):: chemoprotection, bioactivation, gene regulation and genetic polymorphisms

被引:526
作者
Ross, D
Kepa, JK
Winski, SL
Beall, HD
Anwar, A
Siegel, D
机构
[1] Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Denver, CO 80262 USA
[2] Univ Colorado, Hlth Sci Ctr, Ctr Canc, Denver, CO 80262 USA
[3] Univ Montana, Sch Pharm, Dept Pharmaceut Sci, Missoula, MT 59812 USA
关键词
NQO1 (NAD(P)H : quinone oxidoreductase 1); quinone; vitamin E; ubiquinone; antitumor quinones; gene regulation; antioxidant response element (ARE) polymorphisms;
D O I
10.1016/S0009-2797(00)00199-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:77 / 97
页数:21
相关论文
共 151 条
  • [31] Ernster L, 1967, Methods in enzymology, P309, DOI DOI 10.1016/0076-6879(67)10059-1
  • [32] Fourie J, 1999, CLIN CANCER RES, V5, p3781S
  • [33] Novel quinolinequinone antitumor agents:: Structure-metabolism studies with NAD(P)H:quinone oxidoreductase (NQO1)
    Fryatt, T
    Goroski, DT
    Nilson, ZD
    Moody, CJ
    Beall, HD
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (15) : 2195 - 2198
  • [34] NAD(P)H:quinone oxidoreductase:: polymorphisms and allele frequencies in Caucasian, Chinese and Canadian Native Indian and Inuit populations
    Gaedigk, A
    Tyndale, RF
    Jurima-Romet, M
    Sellers, EM
    Grant, DM
    Leeder, JM
    [J]. PHARMACOGENETICS, 1998, 8 (04): : 305 - 313
  • [35] GANOUSIS LG, 1992, MOL PHARMACOL, V42, P1118
  • [36] GIBSON NW, 1992, MOL PHARMACOL, V42, P531
  • [37] Guengerich FP, 1997, COMPREHENSIVE TOXICO, V3, P179
  • [38] Gustafson DL, 1996, MOL PHARMACOL, V50, P728
  • [39] DINITROPYRENE NITROREDUCTASE ACTIVITY OF PURIFIED NAD(P)H-QUINONE OXIDOREDUCTASE - ROLE IN RAT-LIVER CYTOSOL AND INDUCTION BY AROCLOR-1254 PRETREATMENT
    HAJOS, AKD
    WINSTON, GW
    [J]. CARCINOGENESIS, 1991, 12 (04) : 697 - 702
  • [40] PURIFIED NAD(P)H-QUINONE OXIDOREDUCTASE ENHANCES THE MUTAGENICITY OF DINITROPYRENES INVITRO
    HAJOS, AKD
    WINSTON, GW
    [J]. JOURNAL OF BIOCHEMICAL TOXICOLOGY, 1991, 6 (04): : 277 - 282