Human brain tumour cell strains with deficient host-cell reactivation of N-methyl-N′-nitro-N-nitrosoguanidine-damaged adenovirus 5
Human brain tumour cell strains with deficient host-cell reactivation of N-methyl-N′-nitro-N-nitrosoguanidine-damaged adenovirus 5
复制标题
N-甲基-N-硝基-N-亚硝基胍损伤的腺病毒5的宿主细胞再激活缺陷的人脑肿瘤细胞株
作者：
R. Day;C. Ziolkowski
当受损（而非对照）病毒群体的噬斑滴度强烈依赖于选择作为支持病毒生长宿主的细胞株时，则认为发生物理或化学损伤病毒群体的宿主细胞再活化1，2。这种细胞株依赖性的存活差异通常被解释为反映了已知的细胞修复DNA能力的差异1，2。例如，我们以前已经证明了宿主细胞再激活UV照射3或苯并（a）芘二醇-环氧化物I（抗）处理4人腺病毒。当使用具有正常DNA修复的成纤维细胞单层测量它们的噬斑滴度时，这种处理过的病毒群体的存活率比使用来自患有遗传性疾病着色性干皮病的患者的成纤维细胞时高得多，着色性干皮病在修复UV损伤的DNA方面有缺陷。莱特尔及其同事5、6和第3天使用人类细胞的工作表明，只有在研究核复制DNA病毒时，才会发生UV损伤病毒的宿主细胞再活化。为了评估人类肿瘤发生通常与修复缺陷细胞相关的假设，我们进行了一项研究，使用从不同器官的肿瘤和具有遗传易感性或家族性癌症发生的人的皮肤中制备的人类细胞株，对各种损伤的宿主细胞再活化进行了研究。作为这项工作的一部分，我们测量了在体外用致癌物N-甲基-N′-硝基-N-亚硝基胍（MNNG）处理的腺病毒5的存活率。我们发现，使用来自13种人脑肿瘤株中的4种的细胞作为病毒宿主，导致MNNG损伤病毒的存活率低于使用从人类肿瘤或未受影响的人类器官制备的20多种其他细胞株的存活率（图1，表1）。以前的研究没有发现人类肿瘤中异常的DNA修复7。我们相信这是第一个报告的宿主细胞重新激活MNNG损伤的哺乳动物细胞。
HOST-CELL reactivation of a population of physically or chemically damaged viruses is said to occur when the plaque titre of the damaged (but not the control) virus population depends strongly on the cell strain selected to serve as the host to support virus growth1,2. Such cell strain-dependent differences in survival have classically been interpreted as reflecting known cellular differences in ability to repair DNA1,2. For example, we have previously demonstrated host-cell reactivation of UV-irradiated3 or benzo(a)pyrene diol-epoxide I (anti)-treated4 human adenoviruses. The survival of such treated virus populations is much greater when their plaque titre is measured using monolayers of fibroblasts with normal DNA repair than when using fibroblasts from patients having the genetic disease, xeroderma pigmentosum, which are deficient in repair of UV-damaged DNA. The work of Lytle and coworkers5,6 and Day3, using human cells, has shown host-cell reactivation of UV-damaged viruses to occur only when nuclear replicating DNA viruses are studied. To assess the hypothesis that human tumorigenesis is often associated with repair-deficient cells, we undertook a study of host-cell reactivation of various kinds of damage using human cell strains prepared both from tumours of different organs and from skin of people having genetic predisposition to, or familial occurrence of, cancer. As part of this work, we measured the survival of adenovirus 5 treated in vitro with the carcinogen N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We found that the use of cells from 4 of 13 human brain tumour strains as viral hosts resulted in less survival of the MNNG-damaged viruses than did the use of more than 20 other cell strains prepared from human tumours or from unaffected human organs (Fig. 1, Table 1). Previous studies have not detected abnormal DNA repair in human tumours7. We believe this to be the first report of host-cell reactivation of MNNG damage by mammalian cells.