Comparative analysis of the proliferative response of the rat urinary bladder to sodium saccharin by light and scanning electron microscopy and autoradiography.

Three methods used to detect proliferative changes in the rat urothelium, light microscopy, scanning electron microscopy, and autoradiography, were compared for their sensitivity in detecting changes produced by administration of sodium saccharin. Weanling male F344 rats were fed sodium saccharin as 0, 3, 5, or 7.5% of the diet, and the bladders were evaluated after 4, 7, and 10 wks of feeding. Light microscopic changes and an increase in labeling index were seen at all time points in rats fed 7.5% sodium saccharin, but not at the lower doses. A slight increase in labeling index was also observed at 10 wks in the 5.0% group. Scanning electron microscopic changes were evident as early as 4 wks with increasing severity at the 3, 5, and 7.5% doses. This study demonstrates that the hyperplastic response of the urothelium to sodium saccharin administration varies with dose and time, and that observation by scanning electron microscopy is the most sensitive of the three methods evaluated for detecting these changes.