Radioresistance Induced in Rat Embryo Cells by Transfection with the Oncogenes H-ras Plus V-myc is Cell Cycle Dependent and Maximal during S and G₂

Abstract

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 non-transformed 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 radiosensitivity 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.