Department of Radiotherapy, University Hospital Essen, Essen, Germany.
Semin Radiat Oncol. 2010 Oct;20(4):223-31. doi: 10.1016/j.semradonc.2010.05.004.
The rapid phosphorylation of histone H2AX at serine 139 (γH2AX) serves as a sensitive marker for DNA double-strand breaks induced by ionizing radiation or other genotoxic agents. The potential clinical applications of γH2AX detection in tissues from cancer patients during fractionated radiotherapy and the sensitivity for detection of in vivo drug effects on radiation-induced DNA damage responses (DDRs) are discussed. The quantification of γH2AX foci in the nuclei of peripheral blood lymphocytes allows estimation of the applied integral body dose by conformal radiotherapy to tumors in different sites of the body. The limits of precision of biodosimetry in peripheral blood lymphocytes with a γH2AX assay shortly after radiation exposure are shown. The high sensitivity of the in vitro radiation dose-γH2AX foci response allows monitoring of drug effects on DDR pathways after in vivo drug exposure and in vitro irradiation. Drugs are under clinical investigation that modify radiation-induced damage response. If interindividual or intertumoral differences in drug sensitivity exist, the measurement of radiation-induced foci formation and resolution after in vivo drug exposure and in vitro or in vivo irradiation of a cellular probe can serve as a functional assay that may predict the individual gain of a combination therapy. Validation by prospective studies is needed.
组蛋白 H2AX 丝氨酸 139 的快速磷酸化（γH2AX）可作为电离辐射或其他遗传毒性剂诱导的 DNA 双链断裂的敏感标志物。讨论了 γH2AX 在接受分割放疗的癌症患者组织中的检测的潜在临床应用，以及检测体内药物对辐射诱导的 DNA 损伤反应（DDR）的作用的敏感性。外周血淋巴细胞核中 γH2AX 焦点的定量允许通过适形放疗来估计肿瘤在身体不同部位的应用积分体剂量。在辐射暴露后不久进行 γH2AX 测定的外周血淋巴细胞的生物剂量测定精度的限制。体外辐射剂量-γH2AX 焦点反应的高灵敏度允许在体内药物暴露后和体外或体内照射后监测药物对 DDR 途径的作用。正在研究修饰辐射诱导的损伤反应的药物。如果存在个体间或肿瘤间对药物敏感性的差异，则测量体内药物暴露后和体外或体内照射细胞探针后的辐射诱导焦点形成和分辨率，可以作为一种功能测定，预测联合治疗的个体获益。需要前瞻性研究来验证。
