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Evaluation of the tumor-promoting activity of two ß-adrenoreceptor blocking agents, propranolol and atenolol, in liver of Fischer 344 rats
Department of Biology Faculty of Science, University of Milan
3Department of Biomedical Science and Biotechnology Faculty of Medicine, University of Brescia
4General Pathology VI Chair LITA Segrate, Faculty of Medicine, University of Milan, Italy
2Present address: Department of Animal Science Faculty of Veterinary Medicine, University of Padova, Italy
1To whom correspondence should be addressed
The tumor-promoting activity of two ß-adrenoreceptor blocking agents, propranolol and atenolol, was tested in a two-stage protocol of hepatocarcinogenesis in male and female Fischer 344 rats. Propranolol is a lipophlllc non- selective ß-blocker mainly eliminated via the liver; atenolol is a hydrophilic ß1-selective blocking agent, mainly eliniin ated via the kidney. Animals were initiated with a single dose of diethylnitrosamine (DEN, 200 mg/kg, i.p.) and, after 17 days of recovery, were continuously treated with propranolol (75–100 mg/kg) or atenolol (300 mg/kg) by gavage for up to 21 months. Rats given phenobarbital (0.05% in the diet) were used as positive controls. After 2, 4 and 8 months of promotion, preneoplastic lesions were quantified by staining sections of liver for 
-glutamyltrans peptidase (GGT). In non-initiated rats, neither propranolol nor atenolol influenced the development of spontaneous preneoplastic or neoplastic liver lesions. The results obtained in DEN-initiated rats given propranolol cannot be unequivocally interpreted. In the male, propranolol seemed to be ineffective. In the female, there was weak enhancement of DEN-induced GGT foci at 4 and 8 months and of neoplastic lesions thereafter. However, there was great intenindividual variability in focus and tumor yields. Unfortunately, due to the high incidence of liver tumors in rats given DEN alone and the small number of propranolol treated rats that survived until the end of the experiment, no definite conclusion can he drawn about the modifying potential of this ß-blocker on liver carcinogenesis. There was no evidence of liver tumor promotion in DEN-initiated rats of either sex given atenolol.
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