Hilgers G, Abrahams P J, Chen Y Q, Schouten R, Cornelis J J, Lowe J E, van der Eb A J, Rommelaere J
Laboratory of Biophysics and Radiobiology, Université Libre de Bruxelles, Rhode-St-Genèse, Belgium.
Mutagenesis. 1989 Jul;4(4):271-6. doi: 10.1093/mutage/4.4.271.
Radiosensitive fibroblasts from patients with ataxia telangiectasia (AT) were studied for their proficiency in two putative eukaryotic SOS-like responses, namely the enhanced reactivation (ER) and enhanced mutagenesis of damaged viruses infecting pre-irradiated versus mock-treated cells. A previous report indicated that, unlike normal human cells, a line of AT fibroblasts (AT5BIVA) could not be induced to express ER of damaged parvovirus H-1, a single-stranded DNA virus, by UV- or X-irradiation. In the present study, AT5BIVA fibroblasts were also distinguished from normal cells by the inability of the former to achieve enhanced mutagenesis of damaged H-1 virus upon cell UV-irradiation. In contrast, dose-response and time-course experiments revealed normal levels of ER of Herpes simplex virus 1, a double-stranded DNA virus, in X- or UV-irradiated AT5BIVA cells. Taken together, these data point to a possible deficiency of AT cells in a conditioned mutagenic process that contributes to a greater extent to the recovery of damaged single-stranded than double-stranded DNA. Such a defect may concern the replication of damaged DNA or the generation of signals promoting the latter process and may be related to the lack of radiation-induced delay that is typical of AT cell DNA synthesis.
对来自共济失调毛细血管扩张症（AT）患者的放射敏感成纤维细胞进行了研究，以考察它们在两种假定的真核生物SOS样反应中的能力，即增强再活化（ER）以及感染预先辐照细胞与模拟处理细胞的受损病毒的诱变增强。先前的一份报告指出，与正常人细胞不同，一株AT成纤维细胞（AT5BIVA）不能通过紫外线或X射线照射被诱导表达受损细小病毒H-1（一种单链DNA病毒）的ER。在本研究中，AT5BIVA成纤维细胞也与正常细胞不同，因为前者在细胞紫外线照射后不能实现受损H-1病毒诱变增强。相反，剂量反应和时间进程实验显示，在X射线或紫外线照射的AT5BIVA细胞中，双链DNA病毒单纯疱疹病毒1的ER水平正常。综上所述，这些数据表明AT细胞在条件诱变过程中可能存在缺陷，该过程在更大程度上有助于受损单链DNA而非双链DNA的恢复。这种缺陷可能涉及受损DNA的复制或促进后一过程的信号产生，并且可能与AT细胞DNA合成典型的辐射诱导延迟缺乏有关。
