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Establishment of a new laboratory test for radiation sensitivity targeting p53 signal transduction system

建立针对p53信号转导系统的辐射敏感性新实验室测试

基本信息

批准号：
20590580
负责人：
YAMADA Yasuaki
金额：
$ 3.08万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590580/
关键词：
臨床検査医学 p53 放射線 Hzf ATM アポトーシス

项目摘要

Although radiation therapy is one of the effective therapies for cancers, there are some patients who are extraordinarily sensitive to radiation in whom radiation-induced skin ulcer and perforation of gastro-intestinal tracts sometimes occur. Since there is no way to identify such radiation hypersensitive patients before therapy, we tried to establish a laboratory test for this purpose in the present study. Objects are mamma cancer patients who are planned to receive radiation therapy. Peripheral blood mononuclear cells were obtained from these patients before and after radiation. Radiation-induced skin damage was evaluated in all patients, but there was no significant difference among patients, indicating that radiation hypersensitive patients were not included in the study. Absolute peripheral blood lymphocyte count decreased in all patients after radiation, but absolute neutrophil count showed no changes. Interestingly, radiation sensitivity was different among lymphocyte subsets, and T lymphocytes were more sensitive than B lymphocyte or NK lymphocytes. CD8+ T-cell subset was the most sensitive lymphocytes and decrease of the absolute count prolonged even after 12 weeks after radiation. Nevertheless, increase of apoptotic lymphocytes was not observed in the peripheral blood. We then quantified mRNAs of various molecules that are supposed to be influenced by radiation, such as p53, p14ARF、p16INK4A and Hzf. There was however no significant correlation between the changes of the mRNA levels of these molecules and the level of the decrease of absolute lymphocyte counts.

虽然放射治疗是治疗癌症的有效疗法之一，但有些对放射线特别敏感的患者有时会出现放射引起的皮肤溃疡和胃肠道穿孔。由于在治疗前无法识别此类放射过敏患者，因此我们在本研究中尝试为此目的建立实验室测试。对象是计划接受放射治疗的乳腺癌患者。在放射之前和之后从这些患者身上获取外周血单核细胞。对所有患者均评估了放射引起的皮肤损伤，但患者之间没有显着差异，表明放射过敏患者未纳入研究。放疗后所有患者外周血淋巴细胞绝对计数均下降，但中性粒细胞绝对计数无变化。有趣的是，淋巴细胞亚群之间的放射敏感性不同，T淋巴细胞比B淋巴细胞或NK淋巴细胞更敏感。 CD8+ T 细胞亚群是最敏感的淋巴细胞，即使在放疗后 12 周，绝对计数的下降也会延长。然而，在外周血中未观察到凋亡淋巴细胞的增加。然后我们对 p53、p14ARF、p16INK4A 和 Hzf 等可能受辐射影响的各种分子的 mRNA 进行了定量。然而，这些分子的mRNA水平的变化与绝对淋巴细胞计数的减少水平之间没有显着相关性。