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Induction of Hyperplasia and Its Suppression by Hydrocortisone in Organ-cultured Rat Urinary Bladder

Lung Cancer Branch, National Cancer Institute, NIH, Bethesda, Maryland 20014

Urinary bladders from Fischer rats organ cultured in a chemically defined medium, Ham's F12, underwent transitional cell hyperplasia which persisted for the duration of the culture period (10 days). The hyperplastic response was initiated at 2 days of culture in basal epithelial cells as evidenced by [³H]thymidine autoradiography. After 2 days, cells classified as intermediate cells were observed replicating DNA in increasing numbers, whereas the frequency of basal cells replicating DNA decreased. The peak periods of basal and intermediate cell DNA replication were at 2 and 5 days, respectively. The total increase in the number of cells in the epithelium during a 10-day culture period was approximately 2.6-fold. The appearance of DNA-replicating cells before the appearance of mitotic figures indicated that the cells of the transitional epithelium are primarily G₁ cells.

The hyperplastic response in the transitional epithelium was significantly inhibited by hydrocortisone. Epithelia cultured in the presence of hydrocortisone also displayed less atypia than those epithelia cultured in its absence. Hydrocortisone concentrations of 2.1 and 21 µM inhibited hyperplasia by 75 and 84%, respectively. Cells replicating DNA at 2 days of culture were considerably less sensitive to the hydrocortisone inhibition of [³H]thymidine incorporation into DNA than cells replicating DNA at 4 days of culture. The possibility is discussed that basal and intermediate cells may have different sensitivities to hydrocortisone.

Received 10/ 5/76. Accepted 2/10/77.