OXIDATIVE-METABOLISM OF GLUTATHIONE BY GAMMA-GLUTAMYL TRANSPEPTIDASE AND PEROXISOME PROLIFERATION - THE RELEVANCE TO HEPATOCARCINOGENESIS - A HYPOTHESIS

Much has been learned about the function of glutathione (GSH) and other thiols as antioxidants, radioprotectors and radical scavengers. Recent reports point out that GSH and other thiols are double-edged swords: they induce the formation of free radicals and oxidative damage. Such damage is responsible for most, if not all, genotoxicity of GSH to bacteria, and probably to mammalian cells as well. The activation of GSH to an oxidative mutagen and induction of oxidative damage by GSH are catalysed by gamma-glutamyl transpeptidase (GGT), an enzyme appearing very frequently in enzyme-altered foci in livers of rodents, shortly after their exposure to carcinogens. It is proposed here that such GGT-dependent oxidative damage may help in the promotion stage in tumourigenesis, and in that its function may be similar to that of peroxisome proliferators as promotors of hepatocarcinogenesis.