INITIATION OF URINARY-BLADDER CARCINOGENESIS IN RATS BY FREEZE ULCERATION WITH SODIUM SACCHARIN PROMOTION

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (4) , 1469-1473
Abstract
Sodium saccharin induces a significant incidence of transitional cell carcinoma of the bladder when administered to rats either immediately or beginning 2 wk after ulceration of the bladder epithelium induced by freezing or cyclophosphamide injection. However, the marked regenerative hyperplasia following ulceration by either of these methods is not completely repaired until 3-4 wk after ulceration. To determine whether initiation in this model was due to the ulceration and regenerative hyperplasia alone or if it was due to the administration of sodium saccharin acting on the hyperplastic epithelium, the effect of administering sodium saccharin at various times after ulceration was examined. Five week old F344 male rats were given sodium saccharin as 5% of the diet beginning either immediately (group 1) or 2, 4, 6 or 18 wk (groups 2, 3, 4 or 5, respectively) after freezing of the bladder, and sacrificed 2 yr after the start of the experiment. The incidences of rats with transitional cell carcinoma of the bladder were 11 of 36 rats (31%) in group 1, 6 of 36 (17%) in group 2, 12 of 40 (30%) in group 3, 7 of 36 (19%) in group 4 and 9 of 39 (23%) in group 5. Sodium saccharin without prior circulation induced a transitional cell papilloma in 1 rat, and freeze ulceration without subsequent sodium saccharin induced a transitional cell carcinoma in 1 rat. No bladder lesions were seen in the untreated control rats. Scanning electron microscopic examination of rats fed sodium saccharin after ulceration showed evidence of multifocal hyperplasia and significant surface changes either at week 18 of the experiment (groups 1-3) or 18 wk after beginning sodium saccharin administration (groups 4 and 5). Freeze ulceration of the bladder induced irreversible changes in the epithelial cells related to bladder cancer initiation even though the regenerative hyperplasia is morphologically reversible, and sodium saccarain promotes the tumorigenic expression of those freeze ulceration-induced cellular changes even after healing from the injury.

This publication has 1 reference indexed in Scilit: