TY - JOUR
T1 - Chemoprotection against cancer by Phase 2 enzyme induction
AU - Talalay, Paul
AU - Fahey, Jed W.
AU - Holtzclaw, W. David
AU - Prestera, Tory
AU - Zhang, Yuesheng
N1 - Funding Information:
These studiesw ere supportedb y Grants from the National Cancer Institute, Department of Health and Human Services (PO1 CA 44530) and the American Institute for Cancer Research, Washington,D C.
PY - 1995/12
Y1 - 1995/12
N2 - 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 acceptors, 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.
AB - 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 acceptors, 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.
KW - Antioxidant response element (ARE)
KW - Electrophile response element (EpRE)
KW - Glutathione transferases
KW - Quinone reductase
KW - Vegetables
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U2 - 10.1016/0378-4274(95)03553-2
DO - 10.1016/0378-4274(95)03553-2
M3 - Article
C2 - 8597048
AN - SCOPUS:0029558313
SN - 0378-4274
VL - 82-83
SP - 173
EP - 179
JO - Toxicology Letters
JF - Toxicology Letters
IS - C
ER -