DIPHENYL INDUCES UROLITHIASIS BUT DOES NOT POSSESS THE ABILITY TO PROMOTE CARCINOGENESIS BY N-ETHYL-N-HYDROXYETHYLNITROSAMINE IN KIDNEYS OF RATS

Abstract

Chronic toxicity of diphenyl and its ability to promote carcinogenesis by N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the kidney, were studied in Wistar rats. In the study of chronic toxicity, diphenyl at doses of 0, 0.25, and 0.5% was given in the diet to Wistrar rats of both sexes for 75 weeks. Diphenyl dose-dependently induced urolithiasis, and stones, accompanied by hematuria, were observed in the kidney, ureter, and urinary bladder as early as 16 weeks after the beginning of the experiment. At the dose of 0.5% of diphenyl, the incidence of stones in the kidney and urinary bladder was 46.2 and 15.4%, respectively, in females and 31.9 and 27.7%, respectively, in males. Kidney stones were black and composed of protein, but urinary bladder stones were yellowish-white and composed of ammonium magnesium phosphate. In the promotion experiment, EHEN, at a dose of 0.1%, was given in the diet for 2 weeks as the initiator of carcinogenesis, and then diphenyl, at doses of 0, 0.125, and 0.5% was supplied in the diet for 34 weeks, to male Wistar rats. Neither doses of diphenyl affected the incidences of dysplastic foci and renal cell tumors induced by EHEN in the kidney. However, 0.5% of diphenyl, in spite of inducing urolithiasis, significantly decreased the mean numbers of both dysplastic foci and renal cell tumors per cm2 of the kidney. These results indicated that diphenyl induced urolithiasis but exhibited rather inhibitory effect of the induction of kidney carcinogenesis by EHEN in rats.