Day R S, Ziolkowski C H, Scudiero D A, Meyer S A, Lubiniecki A S, Girardi A J, Galloway S M, Bynum G D
Nature. 1980 Dec 25;288(5792):724-7. doi: 10.1038/288724a0.
We have identified a group of 8 (among 39) human tumour cell strains deficient in the ability to support the growth of adenovirus 5 preparations treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but able to support the growth of non-treated adenovirus normally. This deficient behaviour defines the Mer- phenotype. Strains having the Mer- phenotype were found to arise from tumours originating in four different organs. Relative to Mer+ strains, Mer- tumour strains showed greater sensitivity to MNNG-produced killing, greater MNNG-stimulated "DNA repair synthesis and a more rapid MNNG-produced decrease in semi-conservative DNA synthesis. Here we report that (1) Mer- strains are deficient in removing O6-methylguanine (O6-MeG) from their DNA after [Me-14C]MMNG treatment (Table 1); (2) Mer- tumour strains originate from tumours arising in patients having Mer+ normal fibroblasts (Fig. 1a, b); (3) SV40 transformation of (Mer+) human fibroblasts often converts them to Mer- strains (Fig. 1c, d); (4) MNNG produces more sister chromatid exchanges (SCEs) in Mer- than in Mer+ cell strains (Fig. 2).
我们已经鉴定出一组8株（在39株中）人类肿瘤细胞系，它们缺乏支持经N-甲基-N'-硝基-N-亚硝基胍（MNNG）处理的腺病毒5制剂生长的能力，但能够正常支持未处理的腺病毒生长。这种缺陷行为定义了Mer-表型。发现具有Mer-表型的细胞系源自起源于四个不同器官的肿瘤。相对于Mer+细胞系，Mer-肿瘤细胞系对MNNG产生的杀伤表现出更高的敏感性，MNNG刺激的“DNA修复合成”更强，并且MNNG导致的半保留DNA合成下降更快。在此我们报告：（1）Mer-细胞系在经[Me-14C]MMNG处理后从其DNA中去除O6-甲基鸟嘌呤（O6-MeG）的能力存在缺陷（表1）；（2）Mer-肿瘤细胞系源自具有Mer+正常成纤维细胞的患者所患的肿瘤（图1a、b）；（3）（Mer+）人成纤维细胞的SV40转化常常将它们转变为Mer-细胞系（图1c、d）；（4）MNNG在Mer-细胞系中产生的姐妹染色单体交换（SCEs）比在Mer+细胞系中更多（图2）。
