Late G1 accumulation after 2 Gy of γ-irradiation is related to endogenous Raf-1 protein expression and intrinsic radiosensitivity in human cells

Abstract

Summary We have previously reported a correlation between high endogenous expression of the protein product of the RAF-1 protooncogene, intrinsic cellular radiosensitivity and rapid exit from a G/M delay induced by 2 Gy of y-irradiation. Rafl is a positive serine/threonine kinase signal transduction factor that relays signals from the cell membrane to the MAP kinase system further downstream and is believed to be involved in an ionizing radiation signal transduction pathway modulating the G /S checkpoint. We therefore extended our flow cytometric studies to investigate relationships between radiosensitivity, endogenous expression of the Rafl protein and perturbation of cell cycle checkpoints, leading to alterations in the G1, S and G/M populations after 2 Gy of y-irradiation. Differences in intrinsic radiosensitivity after modulation of the GW/S checkpoint have generally been understood to involve p53 function up to the present time. A role for dominant oncogenes in control of G1/S transit in radiation-treated cells has not been identified previously. Here, we show in 12 human in vitro cancer cell lines that late G1 accumulation after 2 Gy of radiation is related to both Rafl expression (r = 0.91, P = 0.0001) and the radiosensitivity parameter SF2 (r = -0.71, P = 0.009).

Overexpression of human Raf‐1 enhances radiosensitivity in fission yeast, Schizosaccharomyces pombe

“…However, consistent with our findings, other laboratories also showed a correlation between high endogenous expression of the Raf-1 protein and rapid exit from cell cycle arrest induced by gamma irradiation in mammalian cells. 27,28 Warenius et al 29,30 showed that endogenous c-raf overexpression was correlated with radiosensitivity rather than radioresistance in 19 human tumour cell lines. In addition, transfection of cultivated urothelial cells HCV-29 cells with v-raf was shown to increase their sensitivity to ionizing radiation.…”