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体外静止和增殖的人肿瘤细胞中辐射诱导的DNA损伤与修复

Radiation-induced DNA damage and repair in quiescent and proliferating human tumor cells in vitro.

作者信息

Wilson K M, Keng P C

机构信息

University of Rochester Cancer Center, NY 14642.

出版信息

Int J Radiat Biol. 1989 Mar;55(3):385-95. doi: 10.1080/09553008914550431.

Abstract

The purpose of this study was to examine radiation-induced DNA strand breakage and repair in quiescent and proliferating human tumor cells in vitro and determine their relationship to radiation sensitivity and potentially lethal damage repair (PLDR). Using centrifugal elutriation we have isolated from fed plateau-phase cultures of HEp-3 human squamous carcinoma cells, relatively pure populations of quiescent and proliferating cells. This was confirmed by both [3H]-thymidine labelling and acridine orange (AO) staining with flow cytometry. Quiescent cells were more sensitive to ionizing radiation (Do = 0.97 Gy) than were proliferating cells (Do = 1.28 Gy). However, quiescent cells showed higher repair of potentially lethal damage (PLDR) than did proliferating cells. Repair of single-strand breaks (ssb) and double-strand breaks (dsb) as measured by filter elution did not differ significantly between quiescent and proliferating cells. For both populations, ssb and dsb repair kinetics and final damage remaining were the same, suggesting that repair of DNA strand breaks is not entirely responsible for the difference in radiation sensitivity between quiescent and proliferating cells.

摘要

本研究的目的是检测体外静止和增殖的人肿瘤细胞中辐射诱导的DNA链断裂及修复情况,并确定它们与辐射敏感性和潜在致死性损伤修复(PLDR)之间的关系。我们使用离心淘析法从处于生长平台期的HEp-3人鳞状癌细胞培养物中分离出相对纯净的静止细胞群和增殖细胞群。通过[3H] - 胸腺嘧啶核苷标记以及吖啶橙(AO)染色结合流式细胞术对此进行了证实。静止细胞比增殖细胞对电离辐射更敏感(Do = 0.97 Gy对Do = 1.28 Gy)。然而,静止细胞显示出比增殖细胞更高的潜在致死性损伤修复(PLDR)能力。通过滤膜洗脱法测定的单链断裂(ssb)和双链断裂(dsb)修复在静止细胞和增殖细胞之间没有显著差异。对于这两种细胞群,ssb和dsb的修复动力学以及最终残留损伤是相同的,这表明DNA链断裂的修复并非静止细胞和增殖细胞之间辐射敏感性差异的完全原因。

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