Effect of urinary pH on the progression of urinary bladder tumours

Systemic alkalosis has been postulated to enhance tumorigenesis, whereas systemic acidosis has been implicated to exert a favourable influence on tumour control and regression. In the present study the urinary pH was influenced by feeding acid-forming or base-forming diets, and the effect of alkaline or acid urine on the early and late progression phase of urinary bladder carcinogenicity was investigated in male Wistar rats. Bladder lesions were initiated by N-butyl-N-(4-hydroxybutyl) nitrosamine (0.05% BBN in the drinking water during 4 weeks) and promoted by sodium bicarbonate (3.4% NaHCO₃ in the diet during 15 or 25 weeks). After short- (15 week) and more long-term (25 week) promotion with NaHCO₃, groups of 20 rats were fed a diet containing the acidifying salt ammoniumchloride (2.1% NH₄Cl) or the control diet. All surviving rats were killed after a total study duration of 52 weeks. Additional control groups were, after initiation, fed diets containing NaHCO₃ and killed after 15 wk or 25 wk of promotion, or at the end of the study. In rats fed diets with added salts, water intake and the amount of urine produced were increased and the urinary density was decreased compared to rats fed control diet. During NaHCO₃ feeding, urinary pH and sodium concentration were increased. During NH₄Cl feeding, urinary pH was decreased and urinary chloride and calcium concentrations were increased. Initiation by BBN followed by treatment with NaHCO₃ caused a high incidence of papillary/nodular hyperplasia, papillomas and carcinomas of the bladder epithelium. These lesions progressed with time or longer duration of NaHCO₃ promotion. A tumour protective effect of urinary acidification by NH₄Cl was not found. In fact, both acidification and prolonged alkalinization tended to aggravate the malignancy of bladder carcinomas.