Changes in the urine and scanning electron microscopically observed appearance of the rat bladder following treatment with tumor promoters.

Urine of rats treated with promoters of urinary bladder carcinogenesis was analyzed during weeks 8 to 24 of administration. The sodium salts of several chemicals, including ascorbic acid, erythorbic acid, acid saccharin and o-phenylphenol increased the urinary pH and sodium ion concentration of the urine. In contrast, treatment with sodium hippurate did not cause elevation of urinary pH although it increased the sodium ion concentration in the urine. Butylated hydroxyanisole, butylated hydroxytoluene (BHT), and ethoxyquin did not affect the urinary pH or any electrolytes except for an increase of phosphorus in the urine of rats given BHT or ethoxyquin. Scanning electron microscopic examination showed that epithelial cells of the urinary bladder of rats given promoters of urinary bladder carcinogenesis had pleomorphic microvilli, short, uniform microvilli, and ropy or leafy microridges on their surfaces. Thus, for the class of promoters including the sodium salts of weak to moderate acids, the elevation of urinary pH and the increase of sodium ion concentration accompany the promoting activity, whereas these changes do not occur following administration of the antioxidant class of bladder tumor promoters.