Strain and sex differences in kidney carcinogenesis in rats treated with N-ethyl-N-hydroxyethylnitrosamine and uracil.

We earlier demonstrated that simultaneous administration of EHEN and uracil for 3 weeks resulted in enhancement of renal carcinogenesis in F344 female rats. Therefore, to establish a model of renal carcinogenesis in rats that can induce advanced renal carcinoma at a high incidence, differences in the susceptibility to N-ethyl-N-hydroxyethylnitrosamine (EHEN) and uracil of the kidneys in male and female rats of two strains were examined. Group 1 (male Wistar rats), group 2 (female Wistar rats), group 3 (male F344 rats), and group 4 (female F344 rats) received a 3-week simultaneous administration of 0.05% EHEN in the drinking water and 3% uracil in the diet after one week's acclimation. In all the above four groups, the rats were thereafter given a basal diet and water without chemical addition for a 29-week period. Group 5 (male Wistar rats), group 6 (female Wistar rats), group 7 (male F344 rats) and group 8 (female F344 rats) received no chemicals for the entire 33 weeks. At the end of the experiment, renal adenocarcinomas were found in 85, 68, 14 and 0% of the rats in groups 1, 2, 3 and 4, respectively. The incidence of adenomas and adenocarcinomas in Wistar rats were significantly greater than in F344 rats (p < 0.0001). These findings indicate strain and possibly sex differences in kidney carcinogenesis in rats treated with EHEN and uracil, and simultaneous administration of the two agents to male Wistar rats might have an advantage for models to induce advanced renal carcinoma at a high incidence.