Wei K, Wandl E, Kärcher K H
University Clinic for Radiotherapy and Radiobiology, University of Vienna, Austria.
Strahlenther Onkol. 1993 Dec;169(12):740-4.
Cell intrinsic radiosensitivity is of great importance in radiation therapy, but its molecular basis is still uncertain. Since DNA double strand breakage is considered to be the most important lesion related to cell death induced by ionizing radiation, the relationship between DNA double-strand breakage, repair and cell survival was investigated in three cell lines: Chinese hamster cell (CHO-K1), human fibroblast and human renal carcinoma (Tu 25). The D0 values after X-irradiation were 1.73, 1.23, and 0.89 Gy, respectively, showing that Tu 25 was the most sensitive among them. DNA double-strand breaks were measured by CHEF electrophoresis, the initial yield of double-strand break per dose in the three cell lines was almost the same, and no correlation to cell survival was found. However, the rejoining capacity for DNA double-strand break differed. After a dose of 20 Gy, the repair rate was markedly lower in Tu 25, with a half repair time of 40 min, as compared with the other two cell lines with half repair times of 15 min. The results strongly supported the correlation between the repair capacity for DNA double-strand break and cell survival. It was concluded that DNA repair capacity is one of the determinants of cell radiosensitivity. Estimation of DNA double-strand break rejoining by CHEF was suggested as a predictive assay for radiosensitivity of human tumor cells.
细胞内在放射敏感性在放射治疗中非常重要，但其分子基础仍不明确。由于DNA双链断裂被认为是与电离辐射诱导的细胞死亡相关的最重要损伤，因此在三种细胞系中研究了DNA双链断裂、修复与细胞存活之间的关系：中国仓鼠细胞（CHO-K1）、人成纤维细胞和人肾癌细胞（Tu 25）。X射线照射后的D0值分别为1.73、1.23和0.89 Gy，表明Tu 25在其中最敏感。通过脉冲场凝胶电泳（CHEF）测量DNA双链断裂，三种细胞系中每剂量双链断裂的初始产率几乎相同，且未发现与细胞存活相关。然而，DNA双链断裂的重新连接能力不同。在20 Gy剂量后，Tu 25的修复率明显较低，半修复时间为40分钟，而其他两种细胞系的半修复时间为15分钟。结果有力地支持了DNA双链断裂修复能力与细胞存活之间的相关性。得出的结论是，DNA修复能力是细胞放射敏感性的决定因素之一。建议通过CHEF估计DNA双链断裂重新连接作为人肿瘤细胞放射敏感性的预测检测方法。
