Mouse Liver Tumors

Peroxisome proliferation in the liver parenchymal cells is frequently observed in rats and mice exposed to certain xenobiotic compounds. Hepatic peroxisome proƯ liferation was first noted nearly twenty years ago in the livers of rats treated with the hypolipidemic drug clofibrate (Hess et aI., 1965; Svoboda and Azarnoff, 1966). Subsequently, several structurally unrelated hypolipidemic compounds were found to induce marked hepatomegaly and hepatic peroxisome proliferation in rats and mice, which led to the suggestion of a possible relationship between peroxisome proliferation and lipid metabolism (Reddy and Krishnakantha, 1975) as well as to the identification of a peroxisomal fatty acid f3-oxidation enzyme sysƯ tem in the rat liver (Lazarow and DeDuve 1976). A second major class of per ox iƯ some proliferators was identified nearly ten years ago, with the discovery that the dietary administration of a widely used phthalate-ester plasticizer di(2-ethylhexƯ yl)phthalate (DEHP) to rats, results in the induction of peroxisomal enzymes in liver (Reddy et aL 1976a). Hypolipidemic drugs and phthalate-ester plasticizers constitute two major and important categories of chemicals with profound peroxisome proliferative property (Reddy et aL 1982; Reddy and Lalwani 1983). These two classes of xenobiotics now have important roles. First, the hypolipiƯ demic drugs are increasingly used in the control of hyperlipidemia, a major risk factor for developing coronary heart disease.