Correlation of dynamic changes in γ-H2AX expression in peripheral blood lymphocytes from head and neck cancer patients with radiation-induced oral mucositis.
Correlation of dynamic changes in γ-H2AX expression in peripheral blood lymphocytes from head and neck cancer patients with radiation-induced oral mucositis.
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DOI：
10.1186/1748-717x-8-155
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发表时间：
2013-06-26
期刊：
影响因子：
--
通讯作者：
Fu S
中科院分区：
文献类型：
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作者：
Li P;Du CR;Xu WC;Shi ZL;Zhang Q;Li ZB;Fu S
评估 γ-H2AX 在外周血淋巴细胞 (PBL) 中的作用，作为接受放射治疗的头颈癌 (HNC) 患者口腔粘膜炎 (OM) 严重程度的预测生物标志物。对 25 名在放疗前接受放疗或放化疗的 HNC 患者抽取的血液样本进行了评估 DNA 损伤和修复动力学的体外测定。至于体内研究，也在放疗前、放疗后第四天和最后一天1小时抽取血样。使用流式细胞术评估 PBL 中 γ-H2AX 的表达。 OM 每周两次使用世界卫生组织 (WHO) 评分进行评估，并与 γ-H2AX 的表达相关。体外检测结果显示，与轻度OM患者相比，重度OM患者在损伤动力学试验中的不同照射剂量下具有较高的γ-H2AX特异性相对荧光，其中8 Gy剂量下的γ-H2AX表达显着较高（p = 0.039），修复动力学试验中2 Gy剂量照射后24小时的γ-H2AX表达也显着高于轻度OM患者（p = 0.008）。照射后 24 小时，γ-H2AX 相对荧光的最佳截止值为 0.960。然而，根据体内测定的评估，两组之间不同时间的 γ-H2AX 表达没有显着差异。这些结果表明，体外研究中来自 PBL 的 γ-H2AX 的损伤和修复动力学可能对于在放疗前确定 HNC 患者的 OM 分级具有预测价值。
To evaluate the role of γ-H2AX in peripheral blood lymphocytes (PBLs) as a predictive biomarker of the severity of oral mucositis (OM) in head and neck cancer (HNC) patients with receiving radiotherapy. In vitro assays for evaluating DNA damage and repair kinetics were performed on blood samples withdrawn from 25 HNC patients undergoing radiotherapy or chemoradiotherapy before radiotherapy. As for the in vivo study, blood samples were also withdrawn before radiotherapy, and 1 hour after radiotherapy on the fourth and last days. Flow cytometry was used to assess the expression of γ-H2AX in PBLs. OM was assessed using the World Health Organization (WHO) scores twice a week and correlated with the expression of γ-H2AX. The in vitro assay results showed that patients with severe OM had higher γ-H2AX-specific relative fluorescence at various irradiation doses in the damage kinetics assay, with significantly higher γ-H2AX expression at 8 Gy (p = 0.039), and also at 24 hours after irradiation at a dose of 2 Gy in the repair kinetics assay, compared to the patients with mild OM (p = 0.008). The optimal cutoff value for relative fluorescence of γ-H2AX was 0.960, 24 hours post-irradiation. However, there were no significant differences in γ-H2AX expression at different times between the two groups, as assessed with the in vivo assay. These results suggest that the damage and repair kinetics of γ-H2AX from PBLs in the in vitro study may have predictive value for identifying the grades of OM among HNC patients prior to radiotherapy.