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Further Studies on the Tumor-Initiating Activity of the Beta-Blocker DL-ZAMI 1305
Department of Biomedical Sciences, Chair of General Pathology, Faculty of Medicine, University of Brescia, 25124 Brescia, Italy
Department of Biomedical Sciences, Chair of General Pathology, Faculty of Medicine, University of Brescia, 25124 Brescia, Italy
Department of Biomedical Sciences, Chair of General Pathology, Faculty of Medicine, University of Brescia, 25124 Brescia, Italy
The purpose of this study was to evaluate the initiating activity of the hepatocarcinogen beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (DL-ZAMI 1305) by the initiation-promotion protocol of Pereira. Female Wistar rats were given a single dose 150 mg/kg of body weight of DL-ZAMI 1305 by gavage 24 hours before or 24 hours after partial hepatectomy. One week later rats were given phenobarbital (0.05%) in the diet for a period of 7 weeks. DL-ZAMI 1305-treatment resulted in the appearance of
Toxicologic Pathology, Vol. 14, No. 4,
470-476 (1986) |
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-glutamyltranspeptidase foci and of other preneoplastic lesions in all animals. Preneoplastic lesions were also present in a fraction of DL-ZAMI 1305-treated animals not subjected to partial hepatectomy, whether given or not phenobarbital. Results obtained in a separate experiment demonstrated that DL-ZAMI 1305-treatment inhibits cell proliferation and induces DNA damage in the regenerating rat liver. The results of this study clearly demonstrated that the beta-blocker DL-ZAMI 1305 is an initiating carcinogen for the liver of female Wistar rats.