Hospital Universitario Virgen de la Victoria, Unidad de Gestión Clínica de Oncología, Málaga, Spain.
Radiother Oncol. 2012 Mar;102(3):450-8. doi: 10.1016/j.radonc.2011.11.002. Epub 2011 Dec 12.
To examine direct and bystander radiation-induced effects in normal umbilical-cord stromal stem cell (HCSSC) lines and in human cancer cells.
The UCSSC lines used in this study were obtained in our laboratory. Two cell lines (UCSSC 35 and UCSSC 37) and two human melanoma skin-cancer cells (A375 and G361) were exposed to ionizing radiation to measure acute radiation-dosage cell-survival curves and radiation-induced bystander cell-death response. Normal cells, although extremely sensitive to ionizing radiation, were resistant to the bystander effect whilst tumor cells were sensitive to irradiated cell-conditioned media, showing a dose-response relationship that became saturated at relatively low doses. We applied a biophysical model to describe bystander cell-death through the binding of a ligand to the cells. This model allowed us to calculate the maximum cell death (χ(max)) produced by the bystander effect together with its association constant (K(By)) in terms of dose equivalence (Gy). The values obtained for K(By) in A375 and G361 cells were 0.23 and 0.29 Gy, respectively.
Our findings help to understand how anticancer therapy could have an additional decisive effect in that the response of sub-lethally hit tumor cells to damage might be required for therapy to be successful because the survival of cells communicating with irradiated cells is reduced.
研究正常脐带间质干细胞（HCSSC）系和人类癌细胞中的直接和旁观者辐射诱导效应。
本研究中使用的 UCSSC 系是在我们的实验室中获得的。将两条细胞系（UCSSC35 和 UCSSC37）和两条人黑色素皮肤癌细胞（A375 和 G361）暴露于电离辐射下，以测量急性辐射剂量细胞存活曲线和辐射诱导的旁观者细胞死亡反应。尽管正常细胞对电离辐射极其敏感，但它们对旁观者效应具有抗性，而肿瘤细胞对辐照细胞条件培养基敏感，表现出剂量反应关系，在相对较低的剂量下达到饱和。我们应用一种生物物理模型来描述通过配体与细胞结合的旁观者细胞死亡。该模型使我们能够计算旁观者效应产生的最大细胞死亡（χ（max））及其关联常数（K（By）），以剂量当量（Gy）表示。在 A375 和 G361 细胞中获得的 K（By）值分别为 0.23 和 0.29 Gy。
我们的研究结果有助于理解抗癌治疗如何产生额外的决定性影响，因为亚致死性打击的肿瘤细胞对损伤的反应可能是治疗成功所必需的，因为与辐照细胞进行通信的细胞的存活减少。
