Quantitative Correlations between Radiosensitivity Biomarkers Show That the ATM Protein Kinase Is Strongly Involved in the Radiotoxicities Observed after Radiotherapy.
Quantitative Correlations between Radiosensitivity Biomarkers Show That the ATM Protein Kinase Is Strongly Involved in the Radiotoxicities Observed after Radiotherapy.
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DOI：
10.3390/ijms231810434
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发表时间：
2022-09-09
影响因子：
5.6
通讯作者：
Foray, Nicolas
中科院分区：
文献类型：
--
作者：
Le Reun, Eymeric;Bodgi, Larry;Granzotto, Adeline;Sonzogni, Laurene;Ferlazzo, Melanie L.;Al-Choboq, Joelle;El-Nachef, Laura;Restier-Verlet, Juliette;Berthel, Elise;Devic, Clement;Bouchet, Audrey;Bourguignon, Michel;Foray, Nicolas
组织过度反应（OR），无论是称为不良反应，放射毒性或放射敏感性反应，可能发生在抗癌放射治疗（RT）期间或之后。它们代表了一个医学、经济和社会问题，并提出了个人对辐射的反应问题。预测和预防它们是放射生物学家的主要任务之一。为此，放射生物学家已经开发了许多涉及不同细胞模型和终点的预测分析。迄今为止，虽然尚未达成共识，认为一种检测方法是OR发生和严重程度的最佳预测因子，但放射肿瘤学家提出了共识量表，以量化6种不同严重程度的OR，无论涉及的器官/组织及其早期/晚期特征如何。不良事件通用术语标准（CTCAE）尤其如此。很少有放射生物学研究使用CTCAE量表作为临床终点，以评价分子和细胞预测试验在人体放射敏感性最大范围内的统计学稳健性。在此，通过使用200个未转化的皮肤成纤维细胞系，这些细胞系来源于在6个CTCAE等级范围内引发OR的RT治疗癌症患者，检查了CTCAE等级与拟定用于预测OR的主要分子和细胞终点（即，2戈伊（SF 2）下的细胞存活率、微核产率、通过免疫荧光与γ H2 AX和pATM标记物评估的识别和未修复DSB）之间的相关性。据我们所知，这是首次在相同队列和照射条件下比较主要放射敏感性终点。无论CTCAE分级范围如何，2戈伊后达到的SF 2和pATM病灶最大数量似乎都是OR的最佳预测因子。所有这些主要的放射敏感性终点在数学上都联系在一个单一的机制模型中，ATM激酶在其中发挥了重要作用的个人对辐射的反应。
Tissue overreactions (OR), whether called adverse effects, radiotoxicity, or radiosensitivity reactions, may occur during or after anti-cancer radiotherapy (RT). They represent a medical, economic, and societal issue and raise the question of individual response to radiation. To predict and prevent them are among the major tasks of radiobiologists. To this aim, radiobiologists have developed a number of predictive assays involving different cellular models and endpoints. To date, while no consensus has been reached to consider one assay as the best predictor of the OR occurrence and severity, radiation oncologists have proposed consensual scales to quantify OR in six different grades of severity, whatever the organ/tissue concerned and their early/late features. This is notably the case with the Common Terminology Criteria for Adverse Events (CTCAE). Few radiobiological studies have used the CTCAE scale as a clinical endpoint to evaluate the statistical robustness of the molecular and cellular predictive assays in the largest range of human radiosensitivity. Here, by using 200 untransformed skin fibroblast cell lines derived from RT-treated cancer patients eliciting OR in the six CTCAE grades range, correlations between CTCAE grades and the major molecular and cellular endpoints proposed to predict OR (namely, cell survival at 2 Gy (SF2), yields of micronuclei, recognized and unrepaired DSBs assessed by immunofluorescence with γH2AX and pATM markers) were examined. To our knowledge, this was the first time that the major radiosensitivity endpoints were compared together with the same cohort and irradiation conditions. Both SF2 and the maximal number of pATM foci reached after 2 Gy appear to be the best predictors of the OR, whatever the CTCAE grades range. All these major radiosensitivity endpoints are mathematically linked in a single mechanistic model of individual response to radiation in which the ATM kinase plays a major role.
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影响因子：
8.8
作者：
Ruiz de Almodovar, J M;Nunez, M I;McMillan, T J;Olea, N;Mort, C;Villalobos, M;Pedraza, V;Steel, G G
通讯作者：
Steel, G G
影响因子：
2.6
作者：
ARLETT, CF;GREEN, MHL;MAYNE, LV
通讯作者：
MAYNE, LV
影响因子：
3.4
作者：
BADIE, C;ILIAKIS, G;MALAISE, EP
通讯作者：
MALAISE, EP
影响因子：
5.6
作者：
Al-Choboq J;Ferlazzo ML;Sonzogni L;Granzotto A;El-Nachef L;Maalouf M;Berthel E;Foray N
通讯作者：
Foray N
影响因子：
8.8
作者：
Badie, C.;Dziwura, S.;Raffy, C.;Tsigani, T.;Alsbeih, G.;Moody, J.;Finnon, P.;Levine, E.;Scott, D.;Bouffler, S.
通讯作者：
Bouffler, S.