Promoting Effect of Sodium L-Ascorbate on N-Butyl-N-(4-hydroxybutyl)nitrosamine-induced Renal Pelvic Carcinogenesis in SD/cShi Rats of Both Sexes

Abstract

Susceptibility to the promoting effects of sodium L-ascorbate (Na-AsA) on the development of pelvis and urinary bladder tumors in male and female SD/cShi rats, featuring spontaneous hydronephrosis, was investigated. Rats received 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and subsequently given basal diet with or without a 5% Na-AsA supplement for 32 weeks. Histopathological examination revealed the promoting effect of Na-AsA on not only the development of urinary bladder tumors but also renal pelvic tumors in the animals of both sexes in this two-stage carcinogenesis experiment, the effect being more prominent in males. Administration of either BBN or Na-AsA alone also induced papillomas and papillary or nodular hyperplasia of renal pelvis or urinary bladder, respectively, in male but not female rats. However, the 5-bromo-2'-deoxyuridine-labeling index of urothelium in the pelvis and bladder increased slightly in male rats and significantly in female rats given Na-AsA alone for 8 weeks. N-butyl-N-(3-carboxypropyl)nitrosamine, which is a metabolite of BBN and proximate carcinogen, was found more in the urine of urinary bladder than that of renal pelvis. These results indicate that the urothelium of the renal pelvis and urinary bladder in SD/cShi rats is susceptible to promoting effects of Na-AsA in the present two stage model urinary tract carcinogenesis, with the urinary bladder of male rats as the most sensitive organ.