Induction of c-myc oncoprotein and of cellular proliferation by radiation in normal human urothelial cultures.

Normal urothelial cultures were established from transplant ureters and irradiated or exposed to nitrosamines. The cells which survived the treatment were monitored for expression of c-myc oncoprotein. The cultures were also exposed to tritiated thymidine (3HTdR) to determine the total number of cells synthesizing DNA. The area of explant outgrowth was also measured. Proliferation is considered to be a fundamental precondition which has to be present before malignant change can take place or which has to accompany this change. The results indicate that the overall growth rate of the carcinogen-treated cultures is relatively faster than that of the controls. This is particularly true one to two weeks after carcinogen exposure. Certain areas of the culture develop abnormally, cells are different in size and shape to the normal uroepithelial cell and have the capacity to pile up and form characteristic foci. These foci continue to proliferate after senescence of control cultures and after senescence of normal areas of treated cultures. The cells in these foci express high levels of c-Myc oncoprotein. Control and treated but normal cells are negative for this antigen under the conditions used. N-ethyl nitrosamine (NEN) (0.005-0.05 micrograms/ml) and radiation (2.5-10.0 Gy) are both able to induce the changes described. The results suggest that radiation and/or nitrosamine treatment can induce uroepithelial cells to divide at a faster rate than usual. Certain cells within this fast growing culture attain the capacity to pile up and acquire a different morphology. These cells do not senescence at the usual time and are c-myc positive. They may represent a subpopulation which has undergone some pre or early malignant changes.