Mouse Liver Tumors : Relevance to Human Cancer Risk Symposium of the European Society of Toxicology Held in Rome, February 2-5, 1986

Peroxisome proliferation in the liver parenchymal cells is frequently observed in rats and mice exposed to certain xenobiotic compounds. Hepatic peroxisome pro­ 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 sys­ tem in the rat liver (Lazarow and DeDuve 1976). A second major class of per ox i­ some proliferators was identified nearly ten years ago, with the discovery that the dietary administration of a widely used phthalate-ester plasticizer di(2-ethylhex­ 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 hypolipi­ demic drugs are increasingly used in the control of hyperlipidemia, a major risk factor for developing coronary heart disease. Front Matter....Pages i-vi Front Matter....Pages 1-1 The Mouse in Safety Evaluation....Pages 3-9 Liver Lesions in B6C3F1 Mice: The National Toxicology Program, Experience and Position....Pages 10-26 Front Matter....Pages 27-27 Invasiveness, Metastasis, and Transplantability of Mouse Liver Nodules....Pages 29-42 Xenobiotic-Induced Peroxisome Proliferation: Role of Tissue Specificity and Species Differences in Response in the Evaluation of the Implications for Human Health....Pages 43-53 The Role of Necrosis in Hepatocellular Proliferation and Liver Tumors....Pages 54-67 Biological Markers Characterizing the Development of Preneoplastic and Neoplastic Lesions in Rodent Liver....Pages 68-80 Relationship Among Histochemically Distinguishable Early Lesions in Multistep-Multistage Hepatocarcinogenesis....Pages 81-94 The Histopathology and Biochemistry of Phenobarbitone-Induced Liver Nodules in C3H Mice....Pages 95-107 Front Matter....Pages 109-109 Species Differences in Enzymes Controlling Reactive Epoxides....Pages 111-124 Species Differences of Glucuronidation and Sulfation in Relation to Hepatocarcinogenesis....Pages 125-135 Glutathione S-Transferase Subunits in the Mouse and Their Catalytic Activities Towards Reactive Electrophiles....Pages 136-146 Species Differences in Biotransformation of and Peroxisome Proliferation Due to Trichloroethylene....Pages 147-147 The Distribution of Carcinogen Metabolizing Enzymes in the Mouse Liver: Comparison of Parenchymal and Non-Parenchymal Cell Populations....Pages 148-156 Investigations on the Mechanism of Liver Tumour Induction by Peroxisome Proliferators....Pages 157-161 DNA Damage and Repair in Mouse Liver....Pages 162-171 Individual Differences in DNA Repair Capacities in Man....Pages 172-179 Variables Influencing DNA-Binding in Mouse Liver....Pages 180-189 Pharmacokinetic Factors and Their Implication in the Induction of Mouse Liver Tumors by Halogenated Hydrocarbons....Pages 190-203 Comparative Study on the Indirect Methylation of Liver DNA Guanine by the 1-Carbon Pool in Hepatotoxicity....Pages 204-216 Activation of a Cellular Proto-Oncogene in Spontaneous Liver Tumor Tissue of the B6C3F1 Mouse....Pages 217-227 Front Matter....Pages 229-229 Nutritional and Dietary Influences on Liver Tumorigenesis in Mice and Rats....Pages 231-243 Anatomy, Function and Aging in the Mouse Liver....Pages 244-250 Sex Hormones and Neoplasia: Liver Tumors in Rodents....Pages 251-263 Sex Hormones and Neoplasia: Genotoxic Effects in Short Term Assays....Pages 264-278 Front Matter....Pages 279-279 Pathogenesis of Experimental Liver Cancer: Comparison with Humans....Pages 281-288 Back Matter....Pages 289-295 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