CHEMOPROTECTION AGAINST CANCER BY PHASE-2 ENZYME-INDUCTION

Mammalian cells have evolved elaborate mechanisms for protection again st the toxic and neoplastic effects of electrophilic metabolites of ca rcinogens and reactive oxygen species. Phase 2 enzymes (e.g. glutathio ne transferase, NAD(P)H:quinone reductase, UDP-glucuronosyltransferase s) and high intracellular levels of glutathione play a prominent role in providing such protection. Phase 2 enzymes are transcriptionally in duced by low concentrations of a wide variety of chemical agents and s uch induction blocks chemical carcinogenesis. The inducers belong to m any chemical classes including phenolic antioxidants, Michael reaction accepters, isothiocyanates, 1,2-dithiole-3-thiones, trivalent arsenic als, HgCl2 and organomercurials, hydroperoxides, and vicinal dimercapt ans. Induction by all classes of inducers involves the antioxidant/ele ctrophile response element (ARE/EpRE). Inducers are widely, but unequa lly, distributed among edible plants. Search for such inducer activity in broccoli led to the isolation of sulforaphane, an isothiocyanate t hat is a very potent Phase 2 enzyme inducer and blocks mammary tumor f ormation in rats.