Influence of beta-adrenergic antagonists on cell proliferation rates in the kidney of untreated and diethylnitrosamine-treated male F344 rats

Some nongenotoxic chemicals which cause kidney tumors have been shown to st imulate tubular cell proliferation. The aim of this study was to evaluate t he effects of two beta-adrenoreceptor blocking agents, propranolol and aten olol, on cell proliferation rates in the kidneys of male F344 rats. Immunoh istochemical expression of proliferating cell nuclear antigen (PCNA) and mi totic index have been examined in formalin-stored kidneys from F344 rats us ed in an initiation-promotion study of carcinogenesis. Cell proliferation r ate was quantified in the proximal tubule epithelium. Non-initiated rats an d rats initiated with a single dose of diethylnitrosamine (DEN, 200 mg/kg, i.p.) were continuously treated with propranolol (75-100 mg/kg) or atenolol (300 mg/kg) by gavage and were sacrificed after 2, 4, 8 or 21 months of ex perimentation. There were two control groups, one untreated (D0) and one gi ven distilled water by gavage (D1). Control group D1 showed significantly l ower cell proliferation rates than the D0 group. In non-initiated rats, pro pranolol had a weak enhancing effect on cell proliferation, mast evident af ter 4 months, while atenolol had a clear enhancing effect most evident afte r 8 months of promoting regimen. Treatment with DEN alone resulted in a sig nificant increase in cell proliferation rate as compared to group D1. In DE N-initiated rats given propranolol, there was a borderline significant incr ease in cell proliferation rates, compared to rats given DEN alone, after 8 months of promoting regimen. Atenolol had no effect. Because of the differ ences in body weight gain and food consumption observed among the various g roups, it is suggested that the state of nutrition may have obscured the ef fects of beta-blockers on cell proliferation rates. (C) 1999 Elsevier Scien ce Ireland Ltd. All rights reserved.