Chromatin Modulation by Histone Deacetylase Inhibitors: Impact on Cellular Sensitivity to Ionizing Radiation.
Chromatin Modulation by Histone Deacetylase Inhibitors: Impact on Cellular Sensitivity to Ionizing Radiation.
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发表时间：
2013
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通讯作者：
F. Carrier
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作者：
F. Carrier
已经确定的是，细胞在细胞周期的G2/M期期间对电离辐射更敏感，此时细胞的染色质高度致密。然而，高度致密的染色质比松弛的染色质对DNA双链断裂（DSB）更不敏感。因此，现在越来越明显的是，细胞修复其受损DNA并将其染色质重新折叠成其原始压实状态的能力主要影响细胞对电离辐射的总体敏感性。组蛋白去乙酰化酶抑制剂（HDACIs）是一类通过增加组蛋白乙酰化水平来松弛染色质结构的新型抗癌剂。HDACIs对正常细胞和癌细胞对电离辐射敏感性的影响不同。有报道表明，HDACIs可以保护正常细胞，同时使癌细胞对电离辐射敏感。这种差异可能源于正常细胞和癌细胞染色质结构的个体特征。这篇综述讨论了这种可能性，并讨论了HDACIs在放射治疗中的作用。
It is well established that cells are more sensitive to ionizing radiation during the G2/M phase of the cell cycle when their chromatin is highly compacted. However, highly compacted chromatin is less susceptible to DNA Double Strand Breaks (DSBs) than relaxed chromatin. Therefore, it is now becoming apparent that it is the cell capacity to repair its damaged DNA and refold its chromatin into its original compacted status that primarily affects the overall cellular sensitivity to ionizing radiation. The Histone Deacetylase Inhibitors (HDACIs) are a new class of anticancer agents that relax chromatin structure by increasing the levels of histone acetylation. The effect of HDACIs on normal and cancer cells sensitivity to ionizing radiation differs. Reports have indicated that HDACIs can protect normal cells while simultaneously sensitize cancer cells to ionizing radiation. This difference may stem from the individual characteristic of the normal and cancer cells chromatin structure. This review discusses this possibility and addresses the role of HDACIs in radiation therapy.