Dose-Dependent Amplification by L-Ascorbic Acid of NaHCO3 Promotion of Rat Urinary Bladder Carcinogenesis

Abstract

The dose dependence of L-ascorbic acid (AsA) copromotion of urinary bladder carcinogenesis with continuous concomitant administration of NaHCO₃ was investigated. In the first experiment, 83 male F344 rats were all given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 wk and then divided into 5 groups, which received basal diet (Oriental MF) containing AsA at 0, 1, 2, 3.5, or 5% plus 1.5% NaHCO₃ for 32 wk. Relative urinary bladder weights in the 5% AsA group were significantly increased as compared to the 0 or 1% group values due to the development of tumors. Both the incidence and number of microscopic urinary bladder lesions (tumors and preneoplastic lesions) showed dose-dependent increases. Furthermore, the sizes of the urinary bladder tumors (carcinomas and papillomas) were significantly increased with the highest dose. 5-bromo-2'-deoxyuridine labeling indices showed slightly increased proliferation in preneoplastic lesions of the urinary bladder epithelium with 5% AsA treatment. In a separate experiment, scanning electron microscopic observation revealed that administration of 5% AsA plus 1.5% NaHCO₃ for 8 wk, without BBN, altered the urinary bladder surface. Elevation of urinary bladder epithelium AsA content, as well as urinary AsA, was also noted. Ornithine decarboxylase (ODC) activity and ODC messenger RNA levels in urinary bladder epithelium of rats treated with 1.5% NaHCO₃ plus 5% AsA for 8 wk showed no statistically significant differences as compared to the control group. The results indicate that AsA amplifies the rat urinary bladder carcinogenesis promotion activity of NaHCO ₃ and that its intensity of action depends on the dose, particularly at high dose.