Diet-induced modification of the acid-base balance in rats: toxicological implications

The composition of the diet can strongly affect the acid-base balance of the body. The studies described in this thesis deal with toxicological implications of dietary modulation of the acid-base balance in rats. These studies included 4-wk, 13-wk and 18-month toxicity studies, and a 30-month carcinogenicity study. Rats were fed a natural ingredient diet (controls), base forming diets (containing 2% or 4% KHCO3), or acid-forming diets (containing 1% or 2.1% NH4Cl). Additional controls were fed 3% KCl (a neutral diet providing K+ and Cl- in amounts equimolar to those in the 4% KHCO3 diet and the 2.1% NH4Cl diet, respectively). In another group of studies the role of the urinary pH and urinary potassium and sodium ions in urinary bladder carcinogenesis was examined. The promoting activities of elevated urinary pH and different urinary electrolyte concentrations in urinary bladder carcinogenesis were studied in an initiation-promotion assay, using N-butyl-N-(4-hydroxybutyl) nitrosamine as tumour initiating agent. In addition, the effects of urinary pH on the early and late progression of experimentally-induced urinary bladder tumours was investigated. In brief, the studies presented in this thesis allowed the following conclusions: · Rats adapted relatively easily to life-long feeding of acidifying or alkalizing diets. Most of the changes induced by the feeding of acid- or base-forming salts may be regarded as physiological adaptations. However, dietary KHCO3 induced oncocytic tubules in the kidneys and neoplastic lesions in the urinary bladder. · Metabolic acidosis did not induce bone loss in rats. · Both potassium and sodium ions were strong mitogenic bladder tumour promotors in rats under conditions of elevated urinary pH, and both ions exerted weak tumour promoting activity when the urine was neutral. · An effect of alkalosis as enhancing factor in tumorigenesis was demonstrated in rats only in the epithelial cells of the urinary bladder where environmental pH can reach very high values in comparison to the systemic pH. This high-dose phenomenon probably carries no relevance to man. · No indications were obtained for a protective effect of chronic systemic acidosis on spontaneous tumour development in rats. · Low environmental pH did not inhibit the progression of experimentally-induced urinary bladder tumours in rats