Hepatotoxicity of agents that enhance formation of focal hepatocellular proliferative lesions (putative preneoplastic foci) in a rapid rat liver bioassay. 1989

J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
Division of Cancer Etiology, National Cancer Institute, Frederick, Maryland 21701-1013.

The histopathology of hepatic toxicity for 58 chemicals previously tested in a rapid rat liver bioassay for demonstrating potential hepatocellular carcinogens and/or tumor promoters was reviewed. Rats received the test diet for 1 week prior to partial hepatectomy and for an additional 5 weeks thereafter at doses near the estimated maximally tolerated dose. These rats served as controls for others receiving initiation by N-nitrosodiethylamine (DEN) and the test diets. Twenty-two of these chemicals were previously found to enhance the formation of glutathione S-transferase, placental form (GST-P)-positive putative preneoplastic hepatocellular foci (promoters) following DEN initiation in this rapid bioassay, whereas 36 chemicals did not. Of the agents that promoted GST-P-positive foci, 14/22 (63.6%) produced toxic hepatocyte lesions while only 4/36 (11.1%) of the nonpromoters did so at the doses used. Biliary toxicity was found for 7/22 (31.8%) of the promoters and 6/36 (16.7%) of the nonpromoters. Only 2/13 (15%) chemicals that inhibited GST-P-positive foci produced hepatic toxicity. Thus, agents that were presumed hepatic tumor promoters characteristically were hepatotoxins while nonpromoters of carcinogenesis were not hepatotoxins in this rapid rat liver bioassay.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008114 Liver Neoplasms, Experimental Experimentally induced tumors of the LIVER. Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008297 Male Males
D011230 Precancerous Conditions Pathological conditions that tend eventually to become malignant. Preneoplastic Conditions,Condition, Preneoplastic,Conditions, Preneoplastic,Preneoplastic Condition,Condition, Precancerous,Conditions, Precancerous,Precancerous Condition
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001681 Biological Assay A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. Bioassay,Assay, Biological,Assays, Biological,Biologic Assay,Biologic Assays,Assay, Biologic,Assays, Biologic,Bioassays,Biological Assays
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D056486 Chemical and Drug Induced Liver Injury A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment. Drug-Induced Liver Injury,Liver Injury, Drug-Induced,Acute Liver Injury, Drug-Induced,Chemically-Induced Liver Toxicity,Drug-Induced Acute Liver Injury,Drug-Induced Liver Disease,Hepatitis, Drug-Induced,Hepatitis, Toxic,Liver Injury, Drug-Induced, Acute,Toxic Hepatitis,Acute Liver Injury, Drug Induced,Chemically Induced Liver Toxicity,Chemically-Induced Liver Toxicities,Disease, Drug-Induced Liver,Diseases, Drug-Induced Liver,Drug Induced Acute Liver Injury,Drug Induced Liver Disease,Drug Induced Liver Injury,Drug-Induced Hepatitides,Drug-Induced Hepatitis,Drug-Induced Liver Diseases,Drug-Induced Liver Injuries,Hepatitides, Drug-Induced,Hepatitides, Toxic,Hepatitis, Drug Induced,Injuries, Drug-Induced Liver,Injury, Drug-Induced Liver,Liver Disease, Drug-Induced,Liver Diseases, Drug-Induced,Liver Injuries, Drug-Induced,Liver Injury, Drug Induced,Liver Toxicities, Chemically-Induced,Liver Toxicity, Chemically-Induced,Toxic Hepatitides,Toxicities, Chemically-Induced Liver,Toxicity, Chemically-Induced Liver

Related Publications

J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
November 1991, Carcinogenesis,
J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
December 1989, Cancer letters,
J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
January 2006, Anticancer research,
J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
February 1984, Carcinogenesis,
J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
April 2010, BMC cancer,
J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
March 1983, Die Naturwissenschaften,
J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
April 1985, Carcinogenesis,
J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
January 1994, Journal of cellular biochemistry. Supplement,
J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
November 1992, Japanese journal of cancer research : Gann,
J M Ward, and H Tsuda, and M Tatematsu, and A Hagiwara, and N Ito
April 1988, Carcinogenesis,
Copied contents to your clipboard!