Increased resistance of peroxisome proliferator-induced hepatic lesions to iron overload in rats

Altered areas (AA), neoplastic nodules (NN) and hepatocellular carcinomas (HCC) induced by chronic administration of ciprofibrate and Wy-14,643 were examined for iron accumulation after systemic iron overload. Eighty percent of AA, 90% NN and 100% HCC showed increased resistance to iron accumulation. However, marked heterogeneity was observed in the amount of iron from area to area within the same lesion with some cells containing no iron, while others showing blue reaction to iron. These findings indicate, that putative preneoplastic and neoplastic hepatic lesions induced by peroxi-some proliferators exclude iron in a fashion similar to that of hepatic nodules and carcinomas induced by DNA damaging carcinogens.