Synchronization of stimulated urothelial proliferation

Summary

In the present experiments an attempt was made to synchronize urothelial proliferation in the urinary bladder of rats stimulated by either a partial cystectomy (one-third resection) or a single i.p. administration (100 mg/kg) of CP. To temporarily inhibit DNA synthesis HU was given intraperitoneally in multiple fractionated doses (0.1 mg/g each) at hourly intervals during the period of most pronounced proliferative activity between 33 and 55 h after partial cystectomy and between 26 and 44 h after injection of CP. Following partial cystectomy the ³H-TdR index rapidly increased after termination of the HU administration reaching peak values of 54% and 56% at 6 and 8 h, respectively. Thereafter, there was a sharp decline of the percentage of DNA synthesizing cells within 2 h to 24% at 10 h. Then 16 h after removal of the HU block the ³H-TdR index amounted to 15%. At 20 h the labeling increased again to 22%, indicating that the initially blocked cells were capable of going through another cell cycle. After 1 week the ³H-TdR index was 2.5% and after 15 days 0.2%. Synchronously with the decrease of DNA synthesis the mitotic index rapidly increased reaching a maximum value of 4.3% at 10 h. The total fraction of ³H-TdR-labeled cells (growth fraction) was 57%. Following administration of CP ³H-TdR incorporation increased steeply after the last injection of HU and at 6 h a maximum value of 50% was obtained. Subsequently, the ³H-TdR index gradually decreased to 11% after 12 h. At 8, 15, and 30 days labeling indices of 1.9%, 0.5%, and 0.3% were determined. The mitotic index was highest with 0.21–0.22% between 12 and 16 h after removal of the HU block. The growth fraction amounted to 53%. The results reported here show a satisfactory degree of synchrony of stimulated urothelial proliferation obtained by multiple fractionated doses of HU. In particular the cystectomy model will be useful for testing possible cell cycle specifity of urothelial carcinogenesis.