Effect of sodium saccharin on urinary bladder epithelial regenerative hyperplasia following freeze ulceration.

Sequential observations of the light and scanning electron microscopic appearances and labeling index of rat urinary bladder epithelium following freeze ulcérationwere 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 ulcération, was investigated. All rats treated with freeze ulcérationof 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 ulcération 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 ulcérationor beginning after 2 weeks of control diet following ulcération, developed nodular and papillary hyperplasia and luminal surface abnormalities detect able 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 re mained elevated. The rats fed control diet without ulcération 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 ulcération. Surprisingly, the development of nodular and papillary lesions detected by light microscopy, surface abnor malities detected by scanning electron microscopy, and in creased labeling index determined by autoradiography were similar to results after sodium saccharin administered immedi ately or beginning 2 weeks after ulcération. The results of these experiments suggest that sodium sac charin prolongs the regenerative hyperplastic changes follow ing ulcération and maintains an increased proliferative rate in the epithelium. These changes appear to contribute to the 1This work was supported in part by USPHS Grant CA 32513 from the National Cancer Institute through the National Bladder Cancer Project. Portions of this work were presented at the 73rd Annual Meeting of the American Association for Cancer Research, St. Louis, Mo.. May 1, 1982 (26). * Present address: First Department of Pathology. Nagoya City University Medical School. Kawasumi. Mizuho-cho, Mizuho-ku. Nagoya 467, Japan. 3 To whom requests for reprints should be addressed, at Department of Pathology and Laboratory Medicine, University of Nebraska Medical Center, 42nd and Dewey Ave., Omaha, Neb. 68105. Received July 8, 1982; accepted October 12. 1982. eventual induction of bladder neoplasms in rats fed sodium saccharin following ulcération.