Abstract
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.
Highlights
We have used Western immunoblotting with semiquantitative densitometry to examine the v-radiation-induced levels of p53 protein in 57 lymphoblastoid cell ines (LCLs) derived from patients with Ataxia telangiectasia (AT), carriers of the AT gene, breast cancer patients and normal donors
We report that AT heterozygote LCLs (n = 5) have a significantly reduced p53 induction when compared with LCls from normal donors (n = 17, P = 0.02)
We found no significant correlation between p53 induction and cellular radiosensitivity in LCLs from breast cancer patients
Summary
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. Studies on human tumour cell lines expressing mutant p53 have shown increased resistance to 7-radiation (Mcllwrath et al, 1994) when compared with lines expressng wild-type p53 They postulate that resistance may result from the inability of the cells to undergo apoptosis. Cells from AT homozygotes show a reduced induction in p53 protein post 7-radiation compared with normal donor cells (Kastan et al, 1992; Nasrin et al, 1994). Lavin et al (1992) showed that AT heterozygotes can be identified by a greaer than normal accumulation of LCLs in G2 phase 24 h post irradiation using a fluorescence-activated cell analyser. Individuals with breast cancer were examined because of the relationship to AT heterozygotes
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