DOSE-DEPENDENT AMPLIFICATION BY L-ASCORBIC-ACID OF NAHCO3 PROMOTION OF RAT URINARY-BLADDER CARCINOGENESIS

The dose dependence of L-ascorbic acid (AsA) copromotion of urinary bl adder carcinogenesis with continuous concomitant administration of NaH CO3 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 a nd 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. Rel ative urinary bladder weights in the 5% AsA group were significantly i ncreased as compared to the 0 or 1% group values due to the developmen t of tumors. Both the incidence and number of microscopic urinary blad der lesions (tumors and prencoplastic lesions) showed dose-dependent i ncreases. Furthermore, the sizes of the urinary bladder tumors (carcin omas and papillomas) were significantly increased with the highest dos e. 5-bromo-2'-deoxyuridine labeling indices showed slightly increased proliferation in preneoplastic lesions of the urinary bladder epitheli um 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 urinar y AsA, was also noted. Ornithine decarboxylase (ODC) activity and ODC messenger RNA levels in urinary bladder epithelium of rats treated wit h 1.5% NaHCO3 plus 5% AsA. for 8 wk showed no statistically significan t differences as compared to the control group. The results indicate t hat AsA amplifies the rat urinary bladder carcinogenesis promotion act ivity of NaHCO, and that its intensity of action depends on the dose, particularly at high dose.