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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Endogenous and radiation-induced expression of gammaH2AX in biopsies from patients treated for carcinoma of the uterine cervix.
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Endogenous and radiation-induced expression of gammaH2AX in biopsies from patients treated for carcinoma of the uterine cervix.

机译：接受过宫颈癌治疗的患者的活检组织中内源性和辐射诱导的gammaH2AX表达。

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BACKGROUND AND PURPOSE: The possibility of using gammaH2AX foci as a marker of DNA damage and as a potential predictor of tumour response to treatment was examined using biopsies from 3 sets of patients with advanced carcinoma of the cervix. The relation between endogenous gammaH2AX expression and hypoxia was also examined. MATERIALS AND METHODS: Set 1 consisted of 26 biopsies that included pre-treatment and 24h post-radiation treatment samples. Pre-treatment biopsies from 12 patients in Set 2 were used to develop image analysis software while pre-treatment biopsies from 33 patients in Set 3 were examined for the relation between staining for the hypoxia marker pimonidazole and endogenous gammaH2AX expression. Formalin-fixed paraffin-embedded sections were analyzed after antigen retrieval and fluorescence antibody labeling for the hypoxia markers CAIX or pimonidazole in combination with gammaH2AX staining. RESULTS: Before treatment, 24+/-19% of cells contained gammaH2AX foci, with most positive cells containing fewer than 5 foci per nucleus. Twenty-four hours after exposure to the first fraction of 1.8-2.5Gy, 38+/-19% contained foci. CAIX positive cells were 1.4 times more likely to exhibit endogenous gammaH2AX foci, and pimonidazole-positive cells were 2.8 times more likely to contain gammaH2AX foci. For 18 patients for whom both pre-treatment and 24h post-irradiation biopsies were available, local control was unrelated to the fraction of cells that retained gammaH2AX foci. However, 24h after irradiation, tumours that had received 2.5Gy showed a significantly higher fraction of cells with residual gammaH2AX foci than tumours given 1.8Gy. CONCLUSIONS: Endogenous gammaH2AX foci are enriched in hypoxic tumour regions. Small differences in delivered dose can produce quantifiable differences in residual DNA damage that can overshadow inter-tumour differences in response.
机译：背景与目的：使用来自3例晚期宫颈癌患者的活组织检查检查了使用gammaH2AX病灶作为DNA损伤的标志物和肿瘤对治疗反应的潜在预测指标的可能性。还检查了内源性gammaH2AX表达与缺氧之间的关系。材料与方法：第一组由26份活检组成，包括放射治疗前和放射治疗后24h。第2组中12例患者的预处理活检被用于开发图像分析软件，而第3组中33例患者的预处理活检被检查缺氧标记物pimonidazole的染色与内源性gammaH2AX表达之间的关系。在抗原回收和荧光抗体标记缺氧标记CAIX或pimonidazole结合gammaH2AX染色后，分析福尔马林固定石蜡包埋的切片。结果：治疗前，有24 +/- 19％的细胞含有gammaH2AX病灶，大多数阳性细胞每个核的病灶少于5个病灶。暴露于第一部分1.8-2.5Gy后二十四小时，有38 +/- 19％的病灶。 CAIX阳性细胞显示内源性gammaH2AX病灶的可能性高1.4倍，而吡莫硝唑阳性细胞含有gammaH2AX病灶的可能性高2.8倍。对于18位既有治疗前又有辐射后24h活检的患者，局部控制与保留gammaH2AX病灶的细胞比例无关。但是，在照射后24小时，接受2.5Gy的肿瘤显示具有残留gammaH2AX灶的细胞比例明显高于接受1.8Gy的肿瘤。结论：内源性γH2AX灶富含缺氧肿瘤区域。递送剂量的微小差异会在残留DNA损伤中产生可量化的差异，从而可能掩盖肿瘤之间的差异。

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