Enhancing Effects of 2-Amino-4,5-diphenylthiazole-Induced Polycystic Kidneys on Renal Carcinogenesis in Rats Treated with Dimethylnitrosamine

• Published in: Toxicology and applied pharmacology Vol. 167; no. 1; pp. 12 - 17
• Main Authors: Takahashi, Satoru, Ikeda, Yoshihisa, Orita, Shin-ichiro, Sakakibara, Michihisa, Kimoto, Naoya, Suzuki, Shugo, Imaida, Katsumi, Shirai, Tomoyuki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2000
• Subjects: 2-amino-4,5-diphenylthiazole; Animals; Body Weight - drug effects; Cytochrome P-450 CYP2E1 - metabolism; Dimethylnitrosamine; Immunohistochemistry; Kidney Neoplasms - chemically induced; Male; Organ Size - drug effects; Polycystic kidney; Polycystic Kidney Diseases - chemically induced; Proliferating Cell Nuclear Antigen - analysis; rat; Rats; Rats, Wistar; renal carcinogenesis; Thiazoles - toxicity; renal carcinogenesis; dimethylnitrosamine; rat; 2-amino-4,5-diphenylthiazole; Polycystic kidney
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.2000.8983

The effects of the polycystic kidney environment on dimethylnitrosamine (DMN)-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 simultaneously administered 1% 2-amino-4,5-diphenylthiazole (DPT) in the diet for 30 weeks. DPT-induced polycystic kidney was associated with a significant increase in the number of renal cell tumors and incidence of mesenchymal tumors in the 25 ppm DMN + DPT group and the incidence of atypical tubules in the 10 ppm DMN + DPT group. PCNA labeling indices of cystic renal tubules in DPT-treated rats were significantly higher than for corresponding noncystic tubules. In Experiment 2, PCNA indices of renal tubules in 10 ppm + DPT rats and immunohistochemically CYP2E1-positive renal tubules in DPT-treated rats were demonstrated to be significantly increased on day 14. CYP2E1 mRNA expression in the kidneys of DPT-treated rats showed a fivefold increase over constitutive levels. The results thus indicate that DPT induction 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.