Prediction of clinical toxicity in localized cervical carcinoma by radio-induced apoptosis study in peripheral blood lymphocytes (PBLs).
Prediction of clinical toxicity in localized cervical carcinoma by radio-induced apoptosis study in peripheral blood lymphocytes (PBLs).
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DOI：
10.1186/1748-717x-4-58
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发表时间：
2009-11-26
期刊：
影响因子：
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通讯作者：
Lloret M
中科院分区：
文献类型：
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作者：
Bordón E;Henríquez Hernández LA;Lara PC;Pinar B;Fontes F;Rodríguez Gallego C;Lloret M
宫颈癌的治疗主要是手术和放射治疗。辐射引起的毒性是治疗成功的限制因素。通过放射诱导的细胞凋亡来测定淋巴细胞的放射敏感性是一种可能的预测性试验开发方法。本研究的目的是分析辐射诱导的外周血淋巴细胞凋亡。94例连续的宫颈癌患者，在我们的机构诊断和治疗，和四个健康对照被纳入研究。使用Lent-Soma量表评价毒性。分离外周血淋巴细胞，分别以0、1、2和8戈伊剂量照射24、48和72 h。使用膜联蛋白V/碘化丙啶通过流式细胞术测量细胞凋亡以确定早期和晚期细胞凋亡。用CD 45 APC偶联的单克隆抗体标记淋巴细胞。辐射诱导的细胞凋亡（RIA）随辐射剂量和孵育时间的增加而增加。放射免疫分析结果符合半对数模型：放射免疫分析（RIA）= βln（戈伊）+ α。该数学模型由两个常数定义：α是Y轴曲线的原点，确定自发细胞死亡的百分比，β是曲线的斜率，确定在确定的辐射剂量下诱导的细胞死亡的百分比（β = ΔRIA/Δln（戈伊））。在低性毒性患者中观察到较高的β值（给定辐射剂量下RIA的增加率）（Exp（B）= 0.83，C.I. 95%（0.73-0.95），p = 0.007; Exp（B）= 0.88，C.I. 95%（0.82-0.94），p = 0.001; Exp（B）= 0.93，C.I. 95%（0.88-0.99），p = 0.026，分别为24、48和72小时）。直肠癌也存在这种关系（Exp（B）= 0.89，C.I. 95%（0.81-0.98），p = 0.026; Exp（B）= 0.95，C.I. 95%（0.91-0.98），p = 0.013，分别为48和72小时）和尿液（Exp（B）= 0.83，C.I. 95%（0.71-0.97），p = 0.021，持续24小时）毒性。在不同的时间点和辐射剂量下，辐射诱导的细胞凋亡符合由数学方程定义的半对数模型，该数学方程给出了放射敏感性的个体值，并可以预测由于放射治疗引起的晚期毒性。需要更多患者的其他前瞻性研究来验证这些结果。
Cervical cancer is treated mainly by surgery and radiotherapy. Toxicity due to radiation is a limiting factor for treatment success. Determination of lymphocyte radiosensitivity by radio-induced apoptosis arises as a possible method for predictive test development. The aim of this study was to analyze radio-induced apoptosis of peripheral blood lymphocytes. Ninety four consecutive patients suffering from cervical carcinoma, diagnosed and treated in our institution, and four healthy controls were included in the study. Toxicity was evaluated using the Lent-Soma scale. Peripheral blood lymphocytes were isolated and irradiated at 0, 1, 2 and 8 Gy during 24, 48 and 72 hours. Apoptosis was measured by flow cytometry using annexin V/propidium iodide to determine early and late apoptosis. Lymphocytes were marked with CD45 APC-conjugated monoclonal antibody. Radiation-induced apoptosis (RIA) increased with radiation dose and time of incubation. Data strongly fitted to a semi logarithmic model as follows: RIA = βln(Gy) + α. This mathematical model was defined by two constants: α, is the origin of the curve in the Y axis and determines the percentage of spontaneous cell death and β, is the slope of the curve and determines the percentage of cell death induced at a determined radiation dose (β = ΔRIA/Δln(Gy)). Higher β values (increased rate of RIA at given radiation doses) were observed in patients with low sexual toxicity (Exp(B) = 0.83, C.I. 95% (0.73-0.95), p = 0.007; Exp(B) = 0.88, C.I. 95% (0.82-0.94), p = 0.001; Exp(B) = 0.93, C.I. 95% (0.88-0.99), p = 0.026 for 24, 48 and 72 hours respectively). This relation was also found with rectal (Exp(B) = 0.89, C.I. 95% (0.81-0.98), p = 0.026; Exp(B) = 0.95, C.I. 95% (0.91-0.98), p = 0.013 for 48 and 72 hours respectively) and urinary (Exp(B) = 0.83, C.I. 95% (0.71-0.97), p = 0.021 for 24 hours) toxicity. Radiation induced apoptosis at different time points and radiation doses fitted to a semi logarithmic model defined by a mathematical equation that gives an individual value of radiosensitivity and could predict late toxicity due to radiotherapy. Other prospective studies with higher number of patients are needed to validate these results.