Peroxisome Proliferation-Related Oxidative Stress and Hepato-Carcinogenesis
Investigation of the phenomenon of xenobiotic-induced peroxisome proliferation in liver parenchymal cells continues to provide fascinating details about the differential regulation of peroxisomal enzymes, their role in the production of intrahepatic oxidative stress and the possible relationship between sustained oxidative stress and the eventual development of hepatocellular carcinomas (1–3), Hepatic peroxisome proliferation was first noted nearly twenty years ago in the livers of rats treated with the hypolipidemic drug Clofibrate (4,5). Subsequently, several structurally diverse chemicals have been identified as hepatic peroxisome proliferators (1,2,6). Long-term feeding studies demonstrated the hepatocarcinogenicity of several of these agents (2,7–9), although they are not genotoxic in short-term tests (10–13). On the basis of these observations it was proposed that peroxisome proliferators form a novel class of chemical carcinogens (8), An understanding of the mechanism of induction of peroxisome proliferation and the metabolic events that accompany persistent increase in the number of these organelles is necessary to resolve the question whether these nongenotoxic hepatocarcinogenic peroxisome proliferators pose the same carcinogenic risk to humans as those that are genotoxic.
KeywordsPeroxisome Proliferators Clofibric Acid Liver Parenchymal Cell Hypolipidemic Drug Peroxisomal Fatty Acid
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