Radioresistance Induced in Rat Embryo Cells by Transfection with the Oncogenes H-rasPlusV-mycis Cell Cycle Dependent and Maximal during S and G2

Rat embryo cells (REC) transformed by the H-ras oncogene plus the cooperating oncogene v-myc are highly resistant to ionizing radiation as compared with the nontransformed parent cells, REC, or immortalized REC. We inquired whether the phenotype of increased radioresistance is maximally expressed in certain phases of the cell cycle. We addressed this question by studying the fluctuations in radio-sensitivity throughout the cycle in an H-ras plus v-myc transformed cell line (3.7), and an immortalized rat embryo cell line (MR). Cells synchronized in various phases of the cell cycle were produced using a combination of elutriation and chemical resynchronization with aphidicolin. The relative radioresistance of 3.7 cells, as compared with MR cells, varied throughout the cell cycle. The two cell lines had similar radiosensitivity when irradiated in G1, or at the G1/S border. However, 3.7 cells progressively developed radioresistance as they progressed into S and remained significantly more radioresistant during the late part of the cell cycle. These observations demonstrate that the radioresistance of 3.7 cells is cell-cycle phase dependent.