Tumor cell radiosensitivity is a major determinant of tumor response to radiation
Tumor cell radiosensitivity is a major determinant of tumor response to radiation
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DOI：
10.1158/0008-5472.can-06-0533
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发表时间：
2006-09-01
期刊：
影响因子：
11.2
通讯作者：
Chen, David J.
中科院分区：
文献类型：
--
作者：
Gerweck, Leo E.;Vijayappa, Shashirekha;Chen, David J.
大量证据表明，肿瘤细胞的辐射敏感性是肿瘤对辐射反应的主要决定因素。最近的研究表明，肿瘤间质的放射敏感性是反应的主要决定因素。为了评估内在肿瘤细胞放射敏感性和肿瘤反应之间的关系，我们改变了克隆肿瘤细胞系的内在放射敏感性，并分析了这种改变对肿瘤反应的影响。用双链断裂修复基因DNA-PKcs转染来自DNA双链断裂修复缺陷型严重联合免疫缺陷小鼠的克隆肿瘤细胞系。转染的肿瘤细胞系的固有放射敏感性降低了1.5倍。使用等基因系在NCr-nu/nu小鼠中引发肿瘤。当移植到相同品系的小鼠中并暴露于相同剂量的辐射时，如果对宿主间质的辐射损伤是反应的主要决定因素，则可以预期同基因肿瘤对辐射表现出类似的反应。这一点没有观察到。在20戈伊的剂量范围内，在4个5-戈伊的部分到30戈伊的单次剂量中，由DNA-PKcs的引入赋予的内在肿瘤细胞辐射抗性的1.5倍增加导致肿瘤生长延迟的1.5倍减少。结果表明，肿瘤细胞的内在放射敏感性是肿瘤对放射反应的主要决定因素。
Substantial evidence suggests that the radiosensitivity of the tumor cells is the primary determinant of tumor response to radiation. More recent studies suggest that tumor stroma radiosensitivity is the principle determinant of response. To assess the relationship between intrinsic tumor cell radiosensitivity and tumor response, we altered the intrinsic radiosensitivity of a cloned tumor cell line and analyzed the effect of this alteration on tumor response. A cloned tumor cell line derived from DNA double-strand break repair-deficient severe combined immunodeficient mice was transfected with the double-strand break repair gene DNA-PKcs. The intrinsic radiosensitivity of the transfected tumor line was decreased by a factor of similar to 1.5. The isogenic lines were used to initiate tumors in NCr-nu/nu mice. When transplanted in the same strain of mice and exposed to the same dose of radiation, the isogenic tumors may be expected to exhibit a similar response to radiation if radiation damage to host stroma is the principle determinant of response. This was not observed. Over the dose range of 20 Gy in four 5-Gy fractions to a single dose of 30 Gy, the 1.5-fold increase in intrinsic tumor cell radioresistance conferred by the introduction of DNA-PKcs caused a 1.5-fold decrease in tumor growth delay. The results show that the intrinsic radiosensitivity of tumor cells is a major determinant of tumor response to radiation.