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Inhibition by the calmodulin antagonist trifluoperazine of experimental hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats. 1996

M Tatsuta, and H Iishi, and M Baba, and H Yano, and H Uehara, and A Nakaizumi, and K Iseki
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.

The effect of the calmodulin antagonist trifluoperazine on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) and on the ornithine decarboxylase (ODC) activity and labeling index of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks, and from the beginning of the experiment, received s.c. injections of 15 or 30 mg/kg body weight of trifluoperazine in depot form every other day until the end of the experiment. Preneoplastic and neoplastic lesions staining positively for glutathione-S-transferase, placental type (GST-P) were examined histochemically. In week 16, quantitative histological analysis showed that prolonged administration of 30 mg but not 15 mg/kg body weight of trifluoperazine resulted in significant reductions in the number and percentage area of GST-P-positive hepatic lesions. Trifluoperazine also caused significant decreases in the ODC activity of the liver and in the labeling indices of enzyme-altered lesions and their adjacent hepatocytes. These findings indicate that trifluoperazine inhibits carcinogenesis and suggest that this effect may be closely related to its effect in inhibiting ODC activity and cell proliferation in the enzyme-altered lesions and their adjacent liver.

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
D009602 Nitrosamines A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. Nitrosamine
D009955 Ornithine Decarboxylase A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated S-adenosylmethionine to form spermidine. Ornithine Carboxy-lyase,Carboxy-lyase, Ornithine,Decarboxylase, Ornithine,Ornithine Carboxy lyase
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
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
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
D014268 Trifluoperazine A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic. Trifluoroperazine,Triftazin,Apo-Trifluoperazine,Eskazine,Flupazine,Stelazine,Terfluzine,Trifluoperazine HCL,Trifluoperazine Hydrochloride,Trifluperazine,Apo Trifluoperazine,ApoTrifluoperazine
D016588 Anticarcinogenic Agents Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved. Anti-Carcinogenic Agents,Anti-Carcinogenic Drugs,Anti-Carcinogenic Effect,Anti-Carcinogenic Effects,Anticarcinogenic Drugs,Anticarcinogenic Effect,Anticarcinogenic Effects,Anticarcinogens,Agents, Anti-Carcinogenic,Agents, Anticarcinogenic,Anti Carcinogenic Agents,Anti Carcinogenic Drugs,Anti Carcinogenic Effect,Anti Carcinogenic Effects,Drugs, Anti-Carcinogenic,Drugs, Anticarcinogenic,Effect, Anti-Carcinogenic,Effect, Anticarcinogenic,Effects, Anti-Carcinogenic,Effects, Anticarcinogenic

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