Chemoprotection against cancer by Phase 2 enzyme induction

被引：390

作者：

Talalay, P

Fahey, JW

Holtzclaw, WD

Prestera, T

Zhang, YS

机构：

[1] Department of Pharmacology and Molecular Sciences, The Johns Hopklns University School of Medicine, Baltimore, MD 21205

来源：

TOXICOLOGY LETTERS | 1995年 / 82-3卷

关键词：

glutathione transferases; quinone reductase; vegetables; antioxidant response element (ARE); electrophile response element (EpRE);

D O I：

10.1016/0378-4274(95)03553-2

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Mammalian cells have evolved elaborate mechanisms for protection against the toxic and neoplastic effects of electrophilic metabolites of carcinogens and reactive oxygen species. Phase 2 enzymes (e.g. glutathione transferase, NAD(P)H:quinone reductase, UDP-glucuronosyltransferases) and high intracellular levels of glutathione play a prominent role in providing such protection. Phase 2 enzymes are transcriptionally induced by low concentrations of a wide variety of chemical agents and such induction blocks chemical carcinogenesis. The inducers belong to many chemical classes including phenolic antioxidants, Michael reaction accepters, isothiocyanates, 1,2-dithiole-3-thiones, trivalent arsenicals, HgCl2 and organomercurials, hydroperoxides, and vicinal dimercaptans. Induction by all classes of inducers involves the antioxidant/electrophile response element (ARE/EpRE). Inducers are widely, but unequally, distributed among edible plants. Search for such inducer activity in broccoli led to the isolation of sulforaphane, an isothiocyanate that is a very potent Phase 2 enzyme inducer and blocks mammary tumor formation in rats.

引用

页码：173 / 179

页数：7

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