One of the earliest cellular responses to DNA double strand breaks (DSBs) is the phosphorylation of the core histone protein H2AX (termed γH2AX). Persistent γH2AX is the level of γH2AX above baseline, measured at a given time-point beyond which DNA DSBs are normally expected to be repaired (usually persist for days to months). This review summarizes the concept of persistent γH2AX in the context of exogenous source induced DNA DSBs (e.g. ionizing radiation (IR), chemotherapeutic drugs, genotoxic agents), and endogenous γH2AX levels in normal aging and accelerated aging disorders. Summary of the current literature demonstrates the following (i) γH2AX persistence is a common phenomenon that occurs in humans and animals; (ii) nuclei retain persistent γH2AX foci for up to several months after IR exposure, allowing for retrospective biodosimetry; (iii) the combination of various radiosensitizing drugs with ionizing radiation exposure leads to persistent γH2AX response, thus enabling the potential for monitoring cancer patients' response to chemotherapy and radiotherapy as well as tailoring cancer treatments; (iv) persistent γH2AX accumulates in telomeric DNA and in cells undergoing cellular senescence; and (v) increased endogenous γH2AX levels may be associated with diseases of accelerated aging. In summary, measurement of persistent γH2AX could potentially be used as a marker of radiation biodosimetry, evaluating sensitivity to therapeutic genotoxins and radiotherapy, and exploring the association of unrepaired DNA DSBs on telomeres with diseases of accelerated aging.

中文翻译：

---

持久性γH2AX：DNA损伤和衰老的有前途的分子标记。

最早的对DNA双链断裂（DSB）的细胞反应之一是核心组蛋白H2AX（称为γH2AX）的磷酸化。持久性γH2AX是在给定的时间点测量的高于基线的γH2AX的水平，超过该时间点通常预期DNA DSB会被修复（通常持续数天至数月）。这篇综述总结了在正常衰老和加速衰老疾病中外源诱导的DNA DSB（例如电离辐射（IR），化学治疗药物，遗传毒性剂）和内源性γH2AX水平的背景下，持久性γH2AX的概念。现有文献的总结表明以下内容：（i）γH2AX持久性是在人和动物中发生的普遍现象；（ii）核在暴露于IR后最多可保留持久的γH2AX焦点，从而可以进行回顾性生物剂量测定；（iii）多种放射增敏药物与电离放射线的结合导致持续的γH2AX反应，从而有可能监测癌症患者对化学疗法和放射疗法的反应以及定制癌症治疗方法；（iv）持久性γH2AX积累在端粒DNA和经历细胞衰老的细胞中；（v）内源性γH2AX水平升高可能与加速衰老相关。总之，持久性γH2AX的测量可潜在地用作放射生物剂量测定的标志物，评估对治疗性基因毒素和放射疗法的敏感性，并探索端粒上未修复的DNA DSB与加速衰老疾病的关联。从而有可能监测癌症患者对化学疗法和放射疗法的反应以及量身定制癌症治疗方法；（iv）持久性γH2AX积累在端粒DNA和经历细胞衰老的细胞中；（v）内源性γH2AX水平升高可能与加速衰老相关。总之，持久性γH2AX的测量可潜在地用作放射生物剂量测定的标志物，评估对治疗性基因毒素和放射疗法的敏感性，并探索端粒上未修复的DNA DSB与加速衰老疾病的关联。从而有可能监测癌症患者对化学疗法和放射疗法的反应以及量身定制癌症治疗方法；（iv）持久性γH2AX积累在端粒DNA和经历细胞衰老的细胞中；（v）内源性γH2AX水平升高可能与加速衰老相关。总之，持久性γH2AX的测量可潜在地用作放射生物剂量测定的标志物，评估对治疗性基因毒素和放射疗法的敏感性，并探索端粒上未修复的DNA DSB与加速衰老疾病的关联。（v）内源性γH2AX水平升高可能与加速衰老相关。总之，持久性γH2AX的测量可潜在地用作放射生物剂量测定的标志物，评估对治疗性基因毒素和放射疗法的敏感性，并探索端粒上未修复的DNA DSB与加速衰老疾病的关联。（v）内源性γH2AX水平升高可能与加速衰老相关。总之，持久性γH2AX的测量可潜在地用作放射生物剂量测定的标志物，评估对治疗性基因毒素和放射疗法的敏感性，并探索端粒上未修复的DNA DSB与加速老化疾病的关联。