Radiosensitivity in ataxia telangiectasia fibroblasts is not associated with deregulated apoptosis

被引:33
作者
Enns, L
Barley, RDC
Paterson, MC
Mirzayans, R [1 ]
机构
[1] Cross Canc Inst, Mol Oncol Program, Edmonton, AB T6G 1Z2, Canada
[2] Univ Alberta, Dept Oncol, Edmonton, AB T6G 1Z2, Canada
[3] King Faisal Specialist Hosp & Res Ctr, Dept Biol & Med Res, Riyadh 11211, Saudi Arabia
关键词
D O I
10.2307/3579639
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Ataxia telangiectasia (AT) is an autosomal recessive human disorder featuring diverse clinical abnormalities including proneness to cancer and extreme sensitivity to ionizing radiation. Although cells from AT patients exhibit faulty activation of the p53 signal transduction pathway at early times after radiation exposure, it has been proposed that high levels of DNA damage persisting in AT cells may up-regulate p53 through an ATM-independent mechanism at late times after irradiation, leading to cell death by apoptosis. In this study we demonstrate that diploid skin fibroblast strains homozygous for the AT mutation fail to up-regulate p53 protein at late times (less than or equal to 48 h) after irradiation with Co-60 gamma rays. Moreover, exposure of normal and AT fibroblasts to a dose of 8 Gy does not result in a significant increase in the fraction of apoptotic cells. Since this treatment reduces the clonogenic potential of human cells by at least two orders of magnitude, we conclude that apoptosis is not the primary mechanism of cell death induced by ionizing radiation in human normal and AT fibroblast cultures. Therefore, our results are not in accordance with the current hypothesis suggesting that increased radiosensitivity of AT cells is associated with deregulated apoptosis. (C) 1998 by Radiation Research Society.
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页码:11 / 16
页数:6
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