Enhancing effects of 2-amino-4,5-diphenylthiazole-induced polycystic kidneys on renal carcinogenesis in rats treated with dimethylnitrosamine

The effects of the polycystic kidney environment on dimethylnitrosamine (DM N)-induced renal carcinogenesis were investigated in rats. In Experiment 1, male Wistar rats were given 25 or 10 ppm DMN in their drinking water and s imultaneously administered 1% 2-amino-4,5-diphenylthiazole (DPT) in the die t for 30 weeks, DPT-induced polycystic kidney was associated with a signifi cant increase in the number of renal cell tumors and incidence of mesenchym al tumors in the 25 ppm DMN + DPT group and the incidence of atypical tubul es in the 10 ppm DMN + DPT group. PCNA labeling indices of cystic renal tub ules in DPT-treated rats were significantly higher than for corresponding n oncystic tubules, In Experiment 2, PCNA indices of renal tubules in 10 ppm + DPT rats and immunohistochemically CYP2E1-positive renal tubules in DPT-t reated rats were demonstrated to be significantly increased on day 14, CYP2 E1 mRNA expression in the kidneys of DPT-treated rats showed a fivefold inc rease over constitutive levels. The results thus indicate that DPT inductio n of polycystic kidneys enhances DMN-induced renal carcinogenesis in rats, with DPT-induced elevated cell proliferation and CYP2E1 expression in renal tubules as possible underlying mechanisms. (C) 2000 Academic Press.