Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Spain.
Radiat Oncol. 2010 Sep 24;5:85. doi: 10.1186/1748-717X-5-85.
DNA-damage assays, quantifying the initial number of DNA double-strand breaks induced by radiation, have been proposed as a predictive test for radiation-induced toxicity. Determination of radiation-induced apoptosis in peripheral blood lymphocytes by flow cytometry analysis has also been proposed as an approach for predicting normal tissue responses following radiotherapy. The aim of the present study was to explore the association between initial DNA damage, estimated by the number of double-strand breaks induced by a given radiation dose, and the radio-induced apoptosis rates observed.
Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radio-induced apoptosis at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide.
Radiation-induced apoptosis increased in order to radiation dose and data fitted to a semi logarithmic mathematical model. A positive correlation was found among radio-induced apoptosis values at different radiation doses: 1, 2 and 8 Gy (p < 0.0001 in all cases). Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). A statistically significant inverse correlation was found between initial damage to DNA and radio-induced apoptosis at 1 Gy (p = 0.034). A trend toward 2 Gy (p = 0.057) and 8 Gy (p = 0.067) was observed after 24 hours of incubation.
An inverse association was observed for the first time between these variables, both considered as predictive factors to radiation toxicity.
DNA 损伤检测，通过量化辐射诱导的 DNA 双链断裂初始数量，被提议作为辐射诱导毒性的预测性检测。通过流式细胞术分析外周血淋巴细胞中的辐射诱导凋亡，也被提议作为预测放疗后正常组织反应的一种方法。本研究的目的是探讨初始 DNA 损伤与观察到的辐射诱导凋亡率之间的关联，该初始 DNA 损伤由特定辐射剂量诱导的双链断裂数量来估计。
从 26 名局部晚期乳腺癌患者中采集外周血淋巴细胞。淋巴细胞的放射敏感性通过每 Gy 和每 DNA 单位（200 Mbp）诱导的双链断裂数量来量化。通过流式细胞术使用 Annexin V/碘化丙啶测量 1、2 和 8 Gy 时的辐射诱导凋亡。
辐射诱导凋亡随着辐射剂量的增加而增加，数据拟合到半对数数学模型中。在不同的辐射剂量下，发现辐射诱导凋亡值之间存在正相关：1、2 和 8 Gy（在所有情况下均 p < 0.0001）。获得的平均 DSB/Gy/DNA 单位为 1.70 ± 0.83（范围 0.63-4.08；中位数，1.46）。在 1 Gy 时，观察到初始 DNA 损伤与辐射诱导凋亡之间存在统计学显著的负相关（p = 0.034）。在孵育 24 小时后，观察到与 2 Gy（p = 0.057）和 8 Gy（p = 0.067）之间的趋势。
首次观察到这些被认为是辐射毒性预测因素的变量之间存在负相关。
