Pacces N, Braga M, Zavanella T, Presta M, Ragnotti G
Toxicol Pathol. 1986;14(4):470-6. doi: 10.1177/019262338601400415.
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.
本研究的目的是通过佩雷拉的启动-促进方案评估肝癌致癌物β受体阻滞剂DL-1-(2-硝基-3-甲基苯氧基)-3-叔丁基氨基丙-2-醇（DL-ZAMI 1305）的启动活性。在部分肝切除术前24小时或术后24小时，通过灌胃给予雌性Wistar大鼠单剂量150 mg/kg体重的DL-ZAMI 1305。一周后，给大鼠喂食含苯巴比妥（0.05%）的饲料，持续7周。用DL-ZAMI 1305处理导致所有动物出现γ-谷氨酰转肽酶灶和其他癌前病变。在未进行部分肝切除术的部分接受DL-ZAMI 1305处理的动物中，无论是否给予苯巴比妥，也都存在癌前病变。在另一项实验中获得的结果表明，用DL-ZAMI 1305处理可抑制再生大鼠肝脏中的细胞增殖并诱导DNA损伤。本研究结果清楚地表明，β受体阻滞剂DL-ZAMI 1305是雌性Wistar大鼠肝脏的一种启动致癌物。
