Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, 26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701, South Korea.
Biochem Biophys Res Commun. 2013 Jan 4;430(1):429-35. doi: 10.1016/j.bbrc.2012.11.040. Epub 2012 Nov 23.
DNA DSBs are induced by IR or radiomimetic drugs such as doxorubicin. It has been indicated that cells from ataxia-telangiectasia patients are highly sensitive to radiation due to defects in DNA repair, but whether they have impairment in apoptosis has not been fully elucidated. A-T cells showed increased sensitivity to high levels of DNA damage, however, they were more resistant to low doses. Normal cells treated with combination of KU55933, a specific ATM kinase inhibitor, and doxorubicin showed increased resistance as they do in a similar manner to A-T cells. A-T cells have higher viability but more DNA breaks, in addition, the activations of p53 and apoptotic proteins (Bax and caspase-3) were deficient, but Akt expression was enhanced. A-T cells subsequently underwent premature senescence after treatment with a low dose of doxorubicin, which was confirmed by G2 accumulation, senescent morphology, and SA-β-gal positive until 15 days repair incubation. Finally, A-T cells are radio-resistant at low doses due to its defectiveness in detecting DNA damage and apoptosis, but the accumulation of DNA damage leads cells to premature senescence.
DNA DSBs 是由 IR 或放射模拟药物如阿霉素诱导的。已经表明，由于 DNA 修复缺陷，共济失调毛细血管扩张症患者的细胞对辐射非常敏感，但它们在凋亡方面是否受损尚未完全阐明。A-T 细胞对高水平的 DNA 损伤表现出更高的敏感性，但对低剂量的辐射更具抵抗力。用特定的 ATM 激酶抑制剂 KU55933 和阿霉素联合处理的正常细胞表现出更高的耐药性，与 A-T 细胞的方式相似。A-T 细胞具有更高的存活率，但更多的 DNA 断裂，此外，p53 和凋亡蛋白（Bax 和 caspase-3）的激活不足，但 Akt 的表达增强。A-T 细胞在用低剂量阿霉素处理后随后经历过早衰老，这通过 G2 积累、衰老形态和 SA-β-gal 阳性得到证实，直到 15 天的修复孵育。最后，A-T 细胞由于其在检测 DNA 损伤和凋亡方面的缺陷而对低剂量辐射具有抗性，但 DNA 损伤的积累导致细胞过早衰老。
