Abstract
The cytotoxic effect of interferons on T24 cells, the established cell line from human urinary bladder cancer, the distribution of the drugs in blood, urine and tissues of various organs and histopathological change in the bladder mucosa in dogs following intravesical instillation of the drugs, were studied. These studies were conducted to investigate the possible application of each type of interferons to intravesical treatment of superfitial bladder cancer. 1) The cytotoxicity of Ro22-8181 (recombinant human interferon alpha), GKT-beta (recombinant human interferon beta) and KW2202 (recombinant human interferon gamma) on T24 cells was examined by colony formation method and growth inhibition assay. Cytocidal effects of interferons were dependent on dose and exposure time, and GKT-beta is most effective (GKT-beta greater than Ro22-8181 greater than KW2202). Cytostatic effects of GKT-beta were also dependent on dose and exposure time. 2) The interferon levels in blood, urine and tissues were measured by FL-Sindbis system following bladder instillation of GKT-beta or KW2202 in beagle dogs with bilateral cutaneous ureterostomy. No interferons were detected in blood and urine. Bladder mucosa and submucosal layer were observed through a microscope 6 and 10 hours after bladder instillation of GKT-beta or KW2202 in beagle dogs with bilateral cutaneous ureterostomy. Degeneration of bladder mucosa and submucosal layer was scarcely observed. The above results suggest that GKT-beta is a suitable drug for intravesical treatment of bladder cancer.
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