Oxidative DNA damage caused by persistent peroxisome proliferation: its role in hepatocarcinogenesis

Abstract

Peroxisome proliferators are considered as a novel class of hepatocarcinogenic agents because of their non-mutagenic nature and their ability to cause a significant increase in the levels of hydrogen peroxide generating peroxisomal fatty acid beta-oxidation enzyme system in the liver. Sustained increase in the number of peroxisomes in liver has been shown to induce oxidative stress in the liver. Increased levels of H2O2 generation, hydroxyl free-radical formation, lipid peroxidation and accumulation of lipofuscin are found in the livers of rats following long-term treatment with peroxisome proliferators. Recent evidence indicates the presence of 8-hydroxydeoxyguanosine in the liver DNA of rats chronically treated with a peroxisome proliferator suggesting that this may be the basis for carcinogenesis by this class of non-mutagenic carcinogens.