Influence of ionizing radiation on proliferation, c-myc expression and the induction of apoptotic cell death in two breast tumour cell lines differing in p53 status

Abstract

Purpose : To determine the capacity of ionizing radiation to inhibit proliferation, 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-MB231 cell line. Materials and methods : Growth inhibition and cell killing were determined by cell number and trypan blue exclusion. Apoptosis was assessed through cell morphology and fluorescent endlabelling. c- myc expression was monitored by Northern blotting. Results : Inhibition of cell proliferation by ionizing radiation was similar in both cell lines. MDA-MB231 cells accumulated in G2 while MCF-7 cells accumulated in both the G1 and G2 phases of the cell cycle after irradiation. There was no evidence of apoptosis in either cell line. In MCF-7 cells, growth inhibition correlated closely with an early dose-dependent suppression of c- myc expression; in MDA-MB231 cells, there was no correspondence between growth inhibition and a transient, dose- independent reduction in c- myc message. Conclusions : These findings suggest that in the absence of classical apoptotic cell death, radiosensitivity is not predictably related to the p53 status of the cell. While both p53 and c- myc may be linked to the DNA damage response pathway, neither p53 nor c- myc are essential for growth arrest in response to ionizing radiation.