Afzal S M, Tenforde T S, Parr S S, Curtis S B
Radiat Res. 1986 Sep;107(3):354-66.
Results are reported of studies to measure the extent of recovery of potentially lethal damage (PLD) in rat rhabdomyosarcoma tumor cells after irradiation both in vivo and in vitro with either high-LET or low-LET radiation. Stationary-phase cultures were found to exhibit repair of PLD following irradiation in vitro either with low-LET X rays or with high-LET neon ions in the extended-peak ionization region. Following a 9-Gy dose of 225-kVp X rays or a 3.5-Gy dose of peak neon ions, both of which reduced the initial cell survival to 6-8%, the maximum PLD recovery factors were 3.4 and 1.6, respectively. In contrast, the standard tumor excision assay procedure failed to reveal any recovery from PLD in tumors irradiated in situ with either X rays or peak neon ions. PLD repair by the in vivo tumor cells could be observed, however, when the excision assay procedure was altered by the addition of a known PLD repair inhibitor beta-arabinofuranosyladenine (beta-ara-A). When a noncytotoxic 50 microM concentration of beta-ara-A was added to the excised tumor cells immediately following a 14.5-Gy in situ dose of X rays, cell survival in the inhibitor-treated cells was lower than in the untreated cells (0.018 compared to 0.056), resulting in a PLD repair inhibition factor of 3.1. Delaying the addition of beta-ara-A for 1, 2, or 3 h following tumor excision reduced the PLD repair inhibition factor to 1.6, 1.5, and 0.9, respectively. Following tumor irradiation in situ with neon ions in the extended-peak ionization region (median LET = 145 keV/micron), less PLD repair was observed than after X irradiation. For 5.8 Gy of peak neon ions, the PLD repair inhibition factors were 2.1, 1.5, 1.3, and 1.1 at 0, 1, 2, and 3 h, respectively. We interpret the absence of measurable PLD repair using the standard tumor excision assay procedure as resulting from undetectable repair occurring during the long interval (about 2 h) required for the cell dissociation and plating procedures. We conclude that at least for our tumor system, PLD repair does occur after irradiation of tumors in situ, even though it is not detectable using the standard tumor excision assay procedure. Thus a failure to measure such repair by this assay in a given tumor system does not necessarily mean the cells are incapable of PLD repair.
报告了关于测量大鼠横纹肌肉瘤肿瘤细胞在体内和体外接受高传能线密度（LET）或低LET辐射后潜在致死性损伤（PLD）恢复程度的研究结果。发现静止期培养物在体外接受低LET X射线或扩展峰电离区域的高LET氖离子照射后会表现出PLD修复。在接受9 Gy的225 kVp X射线剂量或3.5 Gy的峰氖离子剂量后，这两种剂量均使初始细胞存活率降至6 - 8%，最大PLD恢复因子分别为3.4和1.6。相比之下，标准的肿瘤切除试验程序未能揭示在用X射线或峰氖离子原位照射的肿瘤中PLD有任何恢复。然而，当通过添加已知的PLD修复抑制剂β - 阿拉伯呋喃糖基腺嘌呤（β - ara - A）改变切除试验程序时，可以观察到体内肿瘤细胞的PLD修复。在原位接受14.5 Gy X射线剂量后立即向切除的肿瘤细胞中添加非细胞毒性的50 μM浓度的β - ara - A，抑制剂处理的细胞中的细胞存活率低于未处理的细胞（分别为0.018和0.056），导致PLD修复抑制因子为3.1。在肿瘤切除后1、2或3小时延迟添加β - ara - A，PLD修复抑制因子分别降至1.6、1.5和0.9。在用扩展峰电离区域的氖离子原位照射肿瘤后（中位LET = 145 keV/μm），观察到的PLD修复比X射线照射后少。对于5.8 Gy的峰氖离子，在0、1、2和3小时时PLD修复抑制因子分别为2.1、1.5、1.3和1.1。我们将使用标准肿瘤切除试验程序未检测到可测量的PLD修复解释为细胞解离和铺板程序所需的长间隔（约2小时）期间发生了无法检测到的修复。我们得出结论，至少对于我们的肿瘤系统，原位照射肿瘤后确实会发生PLD修复，即使使用标准肿瘤切除试验程序无法检测到。因此，在给定的肿瘤系统中通过该试验未能测量到这种修复并不一定意味着细胞不能进行PLD修复。
