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 (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.
Takahashi
S
S
First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Ikeda
Y
Y
Orita
S
S
Sakakibara
M
M
Kimoto
N
N
Suzuki
S
S
Imaida
K
K
Shirai
T
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004128:Dimethylnitrosamine; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000139:chemically induced*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D007690:Polycystic Kidney Diseases / Q000139:chemically induced*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000633:toxicity*
D018809:Proliferating Cell Nuclear Antigen; D013844:Thiazoles; C002886:Bax 439; D019392:Cytochrome P-450 CYP2E1; D004128:Dimethylnitrosamine