Painter R B, Young B R
Proc Natl Acad Sci U S A. 1980 Dec;77(12):7315-7. doi: 10.1073/pnas.77.12.7315.
The cause of increased radiosensitivity in ataxia-telangiectasia (AT) cells may be a defect in their ability to respond to DNA damage rather than a defect in their ability to repair it. Doses of x-radiation that markedly inhibited the rate of DNA synthesis in normal human cells caused almost no inhibition in AT cells and thus less delay during which x-ray damage could be repaired. The radioresistance of DNA synthesis in AT cells was primarily due to a much smaller inhibition of replicon initiation than in normal cells; the AT cells were also more resistant to damage that inhibited chain elongation. AT cells have been reported to undergo less radiation-induced mitotic delay than normal cells, which may cause them to move from G2 phase into mitosis before repair is complete and may result in the increased incidence of chromatid aberrations observed by others. Therefore, AT cells fail to go through those delays that allow normal cells to repair DNA damage before it can be expressed.
共济失调毛细血管扩张症（AT）细胞放射敏感性增加的原因可能在于其对DNA损伤作出反应的能力存在缺陷，而非修复DNA损伤的能力存在缺陷。能显著抑制正常人细胞DNA合成速率的X射线剂量，对AT细胞几乎没有抑制作用，因此，X射线损伤得以修复的延迟时间更短。AT细胞中DNA合成的放射抗性主要是由于与正常细胞相比，复制子起始受到的抑制要小得多；AT细胞对抑制链延伸的损伤也更具抗性。据报道，与正常细胞相比，AT细胞受到辐射诱导的有丝分裂延迟更少，这可能导致它们在修复完成之前就从G2期进入有丝分裂，可能会导致其他人观察到的染色单体畸变发生率增加。因此，AT细胞不会经历那些能让正常细胞在DNA损伤表达之前进行修复的延迟。
