Further studies on the tumor-initiating activity of the beta-blocker DL-ZAMI 1305.

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 gamma-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.