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.
OBJECTIVE
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.


METHODS
Growth inhibition and cell killing 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
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.
Watson
N C
NC
Department of Medicine and Pharmacology/Toxicology, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298, USA.
Di
Y M
YM
Orr
M S
MS
Fornari
F A
FA
Randolph
J K
JK
Magnet
K J
KJ
Jain
P T
PT
Gewirtz
D A
DA
D017209:Apoptosis / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000528:radiation effects; D004249:DNA Damage; D005260:Female; D016193:G1 Phase; D016259:Genes, myc / Q000528:radiation effects*; D006801:Humans; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D016159:Tumor Suppressor Protein p53