Induction of p53 protein by gamma radiation in lymphocyte lines from breast cancer and ataxia telangiectasia patients.
Exposure of human cells to gamma-radiation causes levels of the tumour-suppressor nuclear protein p53 to increase in temporal association with the decrease in replicative DNA synthesis. Cells from patients with the radiosensitive and cancer-prone disease ataxia telangiectasia (AT) exhibit radioresistant DNA synthesis and show a reduced or delayed gamma-radiation-induced increase in p53 protein levels. We have used Western immunoblotting with semiquantitative densitometry to examine the gamma-radiation-induced levels of p53 protein in 57 lymphoblastoid cell lines (LCLs) derived from patients with AT, carriers of the AT gene, breast cancer patients and normal donors. We confirm the previously reported reduced induction in AT homozygote LCLs (n = 8) compared with normal donor LCLs (n = 17, P = 0.01). We report that AT heterozygote LCLs (n = 5) also have a significantly reduced p53 induction when compared with LCLs from normal donors (n = 17, P = 0.02). The response of breast cancer patient cells was not significantly different from normal donor cells but 18% (5/27) had a p53 response in the AT heterozygote range (95% confidence interval) compared with only 6% (1/17) of the normal donor cells. We found no significant correlation between p53 induction and cellular radiosensitivity in LCLs from breast cancer patients. These methods may be useful in identifying individuals at greater risk of the DNA-damaging effects of ionising radiation.
Birrell
G W
GW
Queensland Radium Institute Research Laboratory, Queensland Institute of Medical Research, Royal Brisbane Hospital, Australia.
Ramsay
J R
JR
D001260:Ataxia Telangiectasia / Q000235:genetics / Q000473:pathology*; D001402:B-Lymphocytes / Q000378:metabolism / Q000528:radiation effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy; D002461:Cell Line, Transformed; D002470:Cell Survival; D004249:DNA Damage; D004261:DNA Replication / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000528:radiation effects; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000528:radiation effects*; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D004854:Herpesvirus 4, Human; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007399:Interphase / Q000528:radiation effects*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53