An hypothesis of the mechanism of urinary bladder tumorigenesis in rat ingesting sodium saccharin.

An hypothesis is presented of a mechanism for the sodium saccharin (NaS)-associated tumorigenesis of the urinary bladder that occurs in male rats. The ingestion of high doses of NaS is associated with increased urine volume and bladder mass. In rats with an inherently high urine output, the diuresis associated with NaS ingestion combined with the increasing diuresis that occurs with age in male rats results in a chronic demand for a bladder-volume increase that is met by excessive cell division of the bladder epithelium. This enhanced mitosis in the bladder epithelium can result in a significant incidence of bladder tumours. Male rats exposed to NaS during early life show an exacerbation of tumour incidence, and it is proposed that this is because the exacerbation of the effects of NaS on the gastro-intestinal and urinary tracts results in increased urine output and bladder hyperplasia in these rats.