Promotion: is saccharin a promoter in the urinary bladder?

A review of various in vivo and in vitro studies indicates that saccharin has second-stage promoting activity in the rat bladder. In vitro, its effect on the human bladder is comparable to that on the rat bladder, and it produces marked hyperplasia of the urothelium. It is clear from the evidence available that the role of saccharin in carcinogenesis of the urinary bladder in vivo is complex. Given before initiation it may possibly act as a co-carcinogen and influence the response of the urothelium to initiating carcinogens. Post-initiation it can cause clonal expansion of preneoplastic cells, thus providing a large population of susceptible cells, which must still undergo some further genetic modification before they can express their full malignant potential. It is possible that saccharin, if present in sufficiently high concentration for a long enough time, may also catalyse this final malignant conversion. Nevertheless, saccharin is not a powerful co-carcinogen or promoting agent by comparison with classical skin promoters such as TPA, and it has been shown to affect tumour prevalence only if present in high concentrations over a prolonged period of time.