COMPARATIVE ANALYSIS OF TWO HUMAN CANCER CELL LINES FOLLOWING EXPOSURE TO LOW DOSE RADIATION

Over the past two decades, studies on the cellular response to very low dose radiation have been revolutionizing historically-held paradigms of cellular radioresponse. Indeed, a host of seemingly contradictory events have recently been reported to occur within this dose range of radiation exposure which make extrapolation of data derived from high dose studies to these low dose ranges no longer a feasible alternative. In this study, we investigate the radioresponse of two human tumor cell lines, A375 human melanoma cells and PC3 human prostate cancer cells, which appear to behave quite differently in the very low dose radiation range. More specifically, we (a) characterize the cell survival response following low dose radiation in the A375 human melanoma cells and PC3 human prostate cancer cell lines; (b) investigate the kinetics and magnitude of cell cycle arrest that occurs following low dose radiation exposure in these cell lines; and (c) ascertain whether signaling through the MAPK and NF-kB proliferative pathways is being stimulated following exposure to low doses of radiation. The results of these studies demonstrate that two different and contradictory survival responses are seen following exposure to very low dose irradiation (hyper-radioresistance in A375 cells vs. hyper-radiosensitivity in PC3 cells). Furthermore, the data indicate that differential regulation of G2/M cell cycle arrest may be involved in the contradictory survival responses observed.  Ph.D