THE INFLUENCE OF THE ONCOGENES NRAS AND MYC ON THE RADIATION SENSITIVITY OF CELLS OF A HUMAN-MELANOMA CELL-LINE

Activation of certain oncogenes may alter the sensitivity of cells to ionizing radiation. We studied the effect of oncogene activation on th e radiation sensitivity of cells of a human melanoma cell line, The ce ll line IGR39D was transfected with the MYC oncogene, the proto-oncoge ne NRAS, NRAS activated by a point mutation (61-arginine) or a combina tion of mutated NRAS and MYC, Single-dose experiments showed a decreas ed survival after transfection with MYC, wild-type NRAS or mutated NRA S, Co-transfection with MYC and mutated NRAS decreased survival up to 4 Gy, whereas at higher doses no shift in radiosensitivity was seen. F low cytometry data indicated that differences in radiosensitivity coul d be explained at least in part by a difference in the distribution of cells in the phases of the cell cycle. After transfection of cells wi th either NRAS or MYC, the number of cells in G(1) phase decreased wit h a concomitant increase of cells in the G(2)/M phase, When the cell l ine transfected with activated NRAS was manipulated so that the distri bution of the cells in the phases of the cell cycle resembled that of the parental line at the time of irradiation, the survival of the cell s was improved, Similar experiments with the cell line containing MYC did not result in an alteration of the distribution of the cells in th e cycle, or the survival after single-dose fractions, suggesting the p resence of a distinct mechanism for influencing radiation sensitivity, Both NRAS and MYC transfection decrease the radiation sensitivity of human melanoma cells, but the underlying mechanisms seem different, In conclusion, transfection with NRAS or MYC alone increases radiation s ensitivity while transfection of cells containing NRAS with MYC restor es resistance at higher doses. (C) 1996 bq Radiation Research Society