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Bladder Calculi and Urothelial Hyperplasia with Papillomatosis in the Rat following Insertion of Chalk Powder in the Bladder Cavity with Subsequent Trauma of the Bladder Wall¹

Cancer Bioassay Laboratory, Department of Pathology, The Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129

A suspension of chalk powder was injected into the cavity of the urinary bladder of Fischer 344 rats. Three weeks later rats were divided into 4 major groups and were given a submucosal injection. One group received a suspension of viable Chapman 4909 tumor cells, the 2nd group received a suspension of frozen-killed 4909 tumor cells, the 3rd group received a suspension of normal rat spleen cells, and the 4th group received cell-free fresh tissue culture medium. After 3 additional weeks urolithiasis was recognized in each experimental group. The incidence of calculi in the groups as listed above was 14 of 17, 6 of 11, 6 of 11, and 2 of 15, respectively.

In control studies inocula consisted of tumor alone, i.e., without chalk powder. Inoculation of the 4909 rat bladder cancer cell line into the lumen of urinary bladders of rats did not result in any calculi after 3 weeks but did produce intramural tumor nodules and hyperplastic changes in adjacent host urothelium in 2 of 10 rats. The tumor inoculated in the submucosa of the bladder produced calculi and papillomas in 2 of 7 rats, and it produced intramural tumor nodules with adjacent hyperplasia of urothelium in all 7 rats.

Over 90% of the rats with large urinary stones, i.e., 35 mg or more, had urothelial changes consisting of both hyperplasia and papillomatosis. For the rats with calculi smaller than 35 mg/rat, hyperplasia was seen in only 25% and no papillomas were observed.

These observations indicate that in the Fischer 344 male rat the formation of calculi in the urinary bladder in association with particles of chalk powder is enhanced by manipulation of the submucosa of the bladder wall by a number of materials. Large calculi themselves, in the absence of neoplastic cells, stimulate the formation of papillomas.

¹ Supported by NIH Research Grants CA 14137 and CA 17772.

² On leave from the Department of Pathology, Nara National Hospital, Higashi Kidera-cho, Nara City, Japan.

³ To whom requests for reprints should be addressed, at Cancer Bioassay Laboratory, Department of Pathology, The Medical College of Pennsylvania, 3300 Henry Avenue, Philadelphia, Pa. 19129.

Received 7/ 7/75. Accepted 9/ 9/75.