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用于测量靶向α粒子疗法旁观者细胞毒性的克隆形成试验。

Clonogenic assay to measure bystander cytotoxicity of targeted alpha-particle therapy.

作者信息

Constanzo Julie, Garcia-Prada Clara Diaz, Pouget Jean-Pierre

机构信息

Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier (ICM), Montpellier, France.

Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier (ICM), Montpellier, France.

出版信息

Methods Cell Biol. 2023;174:137-149. doi: 10.1016/bs.mcb.2022.08.005. Epub 2022 Dec 6.

DOI:10.1016/bs.mcb.2022.08.005
PMID:36710047
Abstract

Radiation therapy induces targeted effects in the cells that are irradiated and also non-targeted effects (i.e. bystander effects) in non-irradiated cells that are close to or at short distance (<∼1 mm) from irradiated cells. Bystander effects are mediated by intercellular communications and may result in cytotoxic and genotoxic modifications. Their occurrence and relative contribution to the irradiation outcome are influenced by several parameters among which the particle linear energy transfer seems to be prominent. Bystander effects were first observed after external radiation therapy, but have been described also following targeted radionuclide therapy. Therefore, we propose a method to investigate their occurrence in experimental conditions where cells are exposed to radiopharmaceuticals. In this approach, clonogenic cell death is the biological endpoint of the bystander effects caused by irradiation with alpha particles (a potent inducer of the bystander response).

摘要

放射治疗在受照射的细胞中诱导靶向效应,同时也在距离受照射细胞较近或距离较短(<约1毫米)的未受照射细胞中诱导非靶向效应(即旁观者效应)。旁观者效应由细胞间通讯介导,可能导致细胞毒性和基因毒性修饰。它们的发生及其对照射结果的相对贡献受几个参数影响,其中粒子线能量转移似乎最为突出。旁观者效应最初是在体外放射治疗后观察到的,但在靶向放射性核素治疗后也有描述。因此,我们提出一种方法来研究在细胞暴露于放射性药物的实验条件下旁观者效应的发生情况。在这种方法中,克隆形成细胞死亡是由α粒子照射(旁观者反应的有效诱导剂)引起的旁观者效应的生物学终点。

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