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

Abstract

各群30匹, 8群合計240匹のラットを用いた.第1～第4群が薬剤投与群, 第5～第8群が薬剤非投与の対照群とした.薬剤投与群には飲料水中に0.05%EHENを, 粉末飼料中に3%ウラシルを混入して, これを3週間同時に投与した.全実験期間は33週間とした.腎腫瘍の発生率は, 第1, 2, 3, 4群でそれぞれ100%, 95%, 71%, 60%であり, WistarラットでF344ラットよりも有意に高率に腎腫瘍の発生がみられた.性差による発生率では, 雄に高率に発生する傾向があったが, 有意差はなかった.対照群には腎腫瘍は発生しなかった.Wistar雄ラットに, EHENとウラシルを同時に投与すれば, 短期間に高頻度に腎腫瘍を誘発させうる

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.