INFLUENCE OF IONIZING-RADIATION ON PROLIFERATION, C-MYC EXPRESSION AND THE INDUCTION OF APOPTOTIC CELL-DEATH IN 2 BREAST-TUMOR CELL-LINES DIFFERING IN P53 STATUS

Purpose: To determine the capacity of ionizing radiation to inhibit pr oliferation, to suppress c-myc expression and to induce apoptotic cell death in the p53 wild-type MCF-7 cell line and the p53 mutated MDA-MB 231 cell line. Materials and methods: Growth inhibition and cell killi ng were determined by cell number and trypan blue exclusion. Apoptosis was assessed through cell morphology and fluorescent end-labelling. c -myc expression was monitored by Northern blotting. Results: Inhibitio n of cell proliferation by ionizing radiation was similar in both cell lines. MDA-MB231 cells accumulated in G(2) while MCF-7 cells accumula ted in both the G(1) and G(2) phases of the cell cycle after irradiati on. There was no evidence of apoptosis in either cell line. In MCF-7 c ells, growth inhibition correlated closely with an early dose-dependen t suppression of c-myc expression; in MDA-MB231 cells, there was no co rrespondence between growth inhibition and a transient, dose-independe nt reduction in c-nye message. Conclusions: These findings suggest tha t in the absence of classical apoptotic cell death, radiosensitivity i s not predictably related to the p53 status of the cell. While both p5 3 and c-myc may be linked to the DNA damage response pathway, neither p53 nor c-myr are essential for growth arrest in response to ionizing radiation.