Sequential observations of the light and scanning electron microscopic appearances and labeling index of rat urinary bladder epithelium following freeze ulceration were performed for 8 weeks, and the effect of sodium saccharin on this process when fed as 5% of the diet, beginning either immediately or 2 weeks after ulceration, was investigated. All rats treated with freeze ulceration of the bladder developed marked nodular and papillary hyperplasia around the ulcer by the fourth day. Under scanning electron microscopy, there were uniform and pleomorphic microvilli on the hyperplastic cell surfaces for the first 14 days after the ulcer. The labeling index of the bladder epithelium ([3H]thymidine injected 1 hr prior to sacrifice) was 10 to 20% after 1 day, and it rapidly diminished to 0.5 to 1.0% by the seventh day. When rats treated with freeze ulceration were fed control diet, the incidence of the light and scanning electron microscopic lesions rapidly diminished after the 14th day, and they were present at very low incidence after 56 days. The labeling index also decreased to the normal level (0.02 to 0.06%) by the 21 st day. In contrast, rats fed sodium saccharin, either immediately after ulceration or beginning after 2 weeks of control diet following ulceration, developed nodular and papillary hyperplasia and luminal surface abnormalities detectable by scanning electron microscopy, and the incidences of these abnormalities remained high for the entire 8 weeks of this experiment. The labeling index in these groups also remained elevated. The rats fed control diet without ulceration had normal bladders. However, rats fed sodium saccharin developed mild simple hyperplasia and an increased labeling index. Another experiment evaluated the effect of delaying the beginning of sodium saccharin administration until 8 weeks after ulceration. Surprisingly, the development of nodular and papillary lesions detected by light microscopy, surface abnormalities detected by scanning electron microscopy, and increased labeling index determined by autoradiography were similar to results after sodium saccharin administered immediately or beginning 2 weeks after ulceration. The results of these experiments suggest that sodium saccharin prolongs the regenerative hyperplastic changes following ulceration and maintains an increased proliferative rate in the epithelium. These changes appear to contribute to the eventual induction of bladder neoplasms in rats fed sodium saccharin following ulceration.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Jan 1 1983|
ASJC Scopus subject areas
- Cancer Research