Induction of XXXX in the bladder epithelium of @entity35 by a dietary excess of acid or base: implications for toxicity/carcinogenicity testing.

@entity8777 @entity1373 @entity400 @entity35 @entity5542
In previous studies we observed an increased incidence of @entity1373 in the epithelium of the urinary bladder of @entity35 fed cereal-based stock diet supplemented with 6% @entity5542 ( @entity5542 ) for 3 months. @entity1373 was not enhanced, however, when 6% @entity5542 was fed in a purified casein diet. Further studies have been conducted to identify the dietary factor that caused the different response with the two diets. Feeding @entity5542 had a marked alkalizing effect on the urine. @entity35 fed purified diet produced urine of higher acidity than did those fed stock diet, a finding attributed to the greater excess of base in the stock diet. When diets with a considerable excess of cations were fed, urinary pH showed a characteristic pattern of widely differing values during a 24-hr period, with high values (pH greater than or equal to 8] for several hours of @entity400 , when food intake was high, declining during the day to a minimum at the end of the light period. @entity1373 of the bladder epithelium was induced not only by feeding @entity5542 , but also by feeding 5% of the alkalizing salt KHCO3, both in purified diet and in stock diet. The epithelial response to an alkalizing substance was prevented by simultaneous feeding of the acidifying salt @entity8777 . These findings indicate that the bladder changes induced by @entity5542 are attributable to its alkalizing properties rather than to @entity5542 per se. Moderate to severe @entity1373 of the bladder epithelium was induced also by feeding 5% @entity8777 in purified diet, a procedure accompanied by a further lowering of urinary pH. These findings showed that @entity1373 of the bladder epithelium of @entity35 can be induced both by acidifying and by alkalizing the urine through manipulation of the acid-base balance of the basal diet. There is thus a possibility that, in carcinogenicity studies, administration of compounds to @entity35 in the form of a salt may lead to erroneous conclusions.
