Abstract
The method of organ culture under hyper-baric oxygen was applied in the present report for they determination of in vitro effects of several anticancer agents onto human bladder carcinomas. Anticancer agents currently being used on clinical cases of bladder carcinoma, such as Mitomycin C, Thio-Tepa and saccharolactone were added to the culture medium at each concentration to be tested. Tissues of transitional cell carcinoma grade 1 to 3 from 21 cases were cultured under 2 atmospheres for 40 hours, temperature at 37°C and pH at 7.2 to 7.4. Cultured tissues were studied histologically, electronmicroscopically and also studied with autoradiography. The autoradiographs were made by 3H-thymidine added to the medium at the last 2 hours of culture period.
In control cultures, tissues from grade 2 of transitional cell carcinoma were well maintained under 2 atmospheres for 48 hours and autoradiographs revealed that the labeling indices of the superficial zone of the explants were higher than the deeper zone where cancer cells were still synthesizing DNA. In cultures with Mitomycin C 1.0mcg per ml, cancer cells near the surface of explants were markedly degenerated, while the cells in deeper zones partly survived and the labeled cells were seen. In cultures with Thio-Tepa 1.0mcg per ml cancer cells of the entire specimen were degenerated. The DNA synthesizing cells were not recognized so far with 3H-thymidine autoradiography of Thio-Tepa group. In cultures with saccharolactone 1.0mcg per ml, the degenerated foci were seen in entire specimens but the degree of degeneration was slight.
By electronmicroscopy, cancer cells near the basement membrane showed deformities of nuclei and nucleoli with a minimum dosis of Thio-Tepa, while the cytoplasmic organellae were affected with Mitomycin C.
The different modes of action of each anticancer agents can be studied with this hyperbaric organ culture system. The results are applicable for the local instillation therapy of carcinoma of the urinary bladder.
