Study on the effects of the hypocholesteremic agents, cholestyramine and compactin on the induction of renal tumors in rats by N-ethyl-N-hydroxyethyl nitrosamine

Abstract

Male Wistar rats were administered with 0.1% N-ethyl-N-hydroxyethyl nitrosamine (EHEN)-containing diet for 2 weeks, and were then Rept for further 23 weeks on basal diet. At 25 weeks, the rats were divided into three groups. Group I was fed on basal diet to 40 weeks. Group II was fed on 2% cholestyramine-containing diet to 40 weeks. Group III was fed on 0.02% compactin-containing diet to 40 weeks. At 40 weeks after the start of experiment, the rats were sacrificed and examined histologically for the incidence of renal cell tumors (RCT) and dysplastic foci (DF) of the kidney. The serum levels of total cholesterol at 40 weeks were 108.9 +/- 23.4, 78.8 +/- 12.5, 95.6 +/- 43.4 mg/dl in Groups I, II and III, respectively. The levels were significantly lower in Groups II and III (p less than 0.01, 0.05, respectively, Wilcoxon test) than Group I. The average numbers of DF were 4.5 +/- 4.1, 1.3 +/- 0.3, 2.3 +/- 2.0 per cm2 of kidney slices in Groups I, II and III, respectively. DF were significantly less in Group II than Group I (p less than 0.025, Wilcoxon test), and less in Group III than Group I (not statistically significant). There was no statistical difference between Groups II and III. RCT were observed in 9 of 34 kidneys (26%), 2 of 18 (11%), 1 of 20 (5%) in Groups, I, II and III, respectively. The ratios of kidneys with RCT were lower in Group II than Group I (not statistically significant), and lower in Group III than Group I (p less than 0.05, qui-square test). There was no statistical difference between Groups II and III. RCT were classified into gross and microscopic lesions. Four gross RCT were found in 4 rats of Group I; no gross RCT was in Groups II and III. There were 5 microscopic RCT in 5 rats, 3 in 2, 1 in 1 in Groups I, II and III, respectively. In Group I, serum levels of total cholesterol were compared between the following subgroups; the rats with RCT and/or with more than 10 DF per kidney, and the rats without RCT and with less than 10 DF per kidney. The mean level was 120.8 +/- 21.8 mg/dl in the former subgroup, which was significantly higher than that (94.1 +/- 19.6 mg/dl) in the latter subgroup (p less than 0.025, Wilcoxon test). The serum cholesterol was suggested to act as a promoter in the development of DF and RCT.