IN-VITRO RADIATION-INDUCED NEOPLASTIC PROGRESSION OF LOW-GRADE UROEPITHELIAL TUMORS

Recent interest has focused on the identification of molecular genetic mechanisms in multistep neoplastic transformation. In vitro exposure of simian virus 40 (SV40)-immortalized human uroepithelial cells (SV-H UC) that are environmentally relevant to bladder carcinogens has been shown to produce tumorigenic transformation, as assessed by the abilit y of cells exposed to a carcinogen to form xenograph tumors with heter ogeneous cancer phenotypes ranging from very aggressive, invasive high -grade carcinomas to superficial low-grade indolent tumors. In additio n, exposure of a low-grade indolent tumor generated in the SV-HUC syst em, MC-T11, to the same carcinogens results in neoplastic progression as assessed by the production of high-grade aggressive cancers. In the present study, we show neoplastic progression of MC-T11 after in vitr o exposure to a single dose of 6 Gy X rays. In addition, we show that the chromosome deletions, including losses of 4q, 11p, 13q and 18, obs erved in these radiation-induced tumors are similar to those observed in carcinogen-induced tumors, thus supporting the hypothesis that the experimental cell system, not the transforming agent, dictates the gen etic losses required for tumorigenic transformation and progression.