Abstract
Promotion effects of sodium L-ascorbate (Na-AsA) on two-stage urinary bladder carcinogenesis were examined in male NCI-Black-Reiter (NBR) rats, which lack a2u-globulin-synthesizing ability, and F344 rats for comparison of the action. The animals were initiated with exposure to 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) via the drinking water for 4 weeks, and then treated with a basal diet containing a 5% supplement of Na-AsA or no added chemical for 32 weeks. The urinary pH and Na ion concentration in both strains of rats treated with BBN followed by Na-AsA (BBN→Na-AsA) were significantly higher than those in the matched controls (BBN alone). Microscopically, significantly increased incidences of papillary or nodular hyperplasia, papillomas, and transitional cell carcinomas were observed in F344 rats treated with BBN →Na-AsA, whereas the incidences of these lesions in NBR rats were comparable in the BBN→Na-AsA and BBN alone cases. These data indicate NBR rats to be resistant to Na-AsA-induced promotion of two-stage urinary bladder carcinogenesis. Since the elevation of urinary parameters generally associated with tumor promotion by Na-AsA was a feature with both strains, another factor such as a2u-globulin, may also be active for enhancement of lesion development.
