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Correlation of dynamic changes in γ-H2AX expression in peripheral blood lymphocytes from head and neck cancer patients with radiation-induced oral mucositis

机译:辐射诱发口腔黏膜炎的头颈癌患者外周血淋巴细胞γ-H2AX表达的动态变化

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Background 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. Methods In vitro assays for evaluating DNA damage and repair kinetics were performed on blood samples withdrawn from 25 HNC patients undergoing radiotherapy or chemoradiotherapy before radiotherapy. As for the in vivo study, blood samples were also withdrawn before radiotherapy, and 1 hour after radiotherapy on the fourth and last days.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. Results 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. Conclusions 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.
机译:背景为了评估γ-H2AX在外周血淋巴细胞(PBLs)中的作用,作为接受放疗的头颈癌(HNC)患者口腔粘膜炎(OM)严重程度的预测生物标志物。方法对25例接受放疗或放化疗的HNC患者在放疗前抽取的血样进行体外DNA损伤和修复动力学评估。至于体内研究,在放疗前和放疗后第4天及最后一天也取了血样。流式细胞仪用于评估PBLs中γ-H2AX的表达。每周两次使用世界卫生组织(WHO)评分评估OM,并与γ-H2AX的表达相关。结果体外试验结果表明,在损伤动力学试验中,重度OM患者在不同剂量的γ-H2AX特异性相对荧光较高,在8 Gy时γ-H2AX表达显着较高(p?=?0.039),并且与轻度OM的患者相比,在修复动力学测定中以2 Gy的剂量照射后24小时也是如此(p?=?0.008)。辐照后24小时,γ-H2AX相对荧光的最佳截止值为0.960。然而,通过体内试验评估,两组之间在不同时间的γ-H2AX表达没有显着差异。结论这些结果表明,体外研究中PBL对γ-H2AX的损伤和修复动力学可能对确定放疗前HNC患者的OM等级具有预测价值。

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