The effect of the nephrotoxic substance, N-(3,5-dichlorophenyl)succinimide, on the histological pattern and incidences of kidney tumors in rats induced by dimethylnitrosoamine was studied histologically. Post-treatment with N-(3,5-dichlorophenyl)succinimide markedly increased the induction of tumors, especially renal cell tumors, by dimethylnitrosoamine, but pretreatment with this substance clearly inhibited the induction of tumors, especially embryonal cell tumors in the kidney. Oral

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... tion of N-(3,5-dichlorophenyl)succinimide alone caused severe interstitial nephritis but not development of kidney tumors. Thus, treatment with N-(3,5-dichlorophenyl)succinimide changes the histological type and incidence of kidney tumors in rats induced by dimethylnitrosoamine. There have been many investigations on experimental conditions for induction of kidney tumors in rats and mice, and on the histology, histogenesis, ultrastructure, biochemistry, and biology of these tumors. [3] [4] [5] [6] [7] [8] [9] [10] [11] [13] [14] [15] [16] 19, 20, 22, 24, 28) Histopathological analysis has been made of kindey tumors in rats induced by various carcinogens.15,27) The kidney tumors in rats induced by dimethylnitrosoamine have been classified into three types; epithelial, mesenchymal, and vascular. Previous reports have shown that dimethylnitrosoamine mainly induces mesenchymal tumors in rat kidney. 15, 19, 24, 27) Recent investigations have also shown that oral administration of a high concentration of N-(3,5-dichlorophenyl)succinimide to rats induces severe interstitial nephritis.17,18) The present paper describes the effect of the nephrotoxic chemical, N-(3,5-dichlorophenyl)succinimide, on the induction of kidney tumors in rats by dimethylnitrosoamine. The effect of this nephrotoxic chemical substance on the histological pattern and incidence of kidney tumors induced by dimethylnitrosoamine was also analyzed histologically. MATERIALS AND METHODS Male Wistar strain rats (Fuji Animal Farm, Tokyo), 8 to 10 weeks old, with an average body weight of 185g, were used. Seventy-four rats were divided into 6 groups. Group 1, Sixteen rats were fed on the semi-synthetic basal diet described previously,14) supplemented with 500ppm of dimethylnitrosoamine (Tokyo Kasei Co., Tokyo) for 2 weeks and then on commercial stock diet (Oriental MF) for 22 weeks. Group 2, Sixteen rats were fed on basal diet containing 500ppm of dimethylnitrosoamine for 2 weeks, on stock diet for 2 weeks, on basal diet containing 5000ppm of N-(3,5-dichlorophenyl)succinimide (Sumitomo Chemical Co., Osaka) for 8 weeks, and then on stock diet for 12 weeks. Group 3, Twelve rats were fed on basal diet for 2 weeks, on stock diet for 2 weeks, on basal diet containing 5000ppm of N-(3,5-dichlorophenyl)succinimide for 8 weeks, and then on stock diet for 12 weeks. Group 4, Twelve rats were fed on basal diet containing 5000ppm of N-(3,5-dichlorophenyl)succinimide for 8 weeks, on stock diet for 2 weeks, on basal diet containing 500ppm of dimethylnitrosoamine for 2 weeks, and then on stock diet for 22 weeks. Group 5, Twelve rats were fed on basal diet containing 5000ppm of N-(3,5-dichlorophenyl)succinimide for 8 weeks, on stock diet for 2 weeks, on basal diet for 2 weeks, and then on stock diet for 22 weeks. Group 6, Six rats were fed on stock diet for 10 weeks, on basal diet for 2 weeks, and then on stock diet for 22 weeks.