Lefebvre P, Zak P, Laval F
Groupe "Radiochimie de l'ADN," Unité 247 INSERM, Institut Gustave Roussy, Villejuif, France.
DNA Cell Biol. 1993 Apr;12(3):233-41. doi: 10.1089/dna.1993.12.233.
The inducibility of two DNA repair proteins, the O6-methylguanine-DNA-methyltransferase (MGMT) and the N3-methyladenine-DNA-glycosylase (ANPG), was studied by measuring the protein activities and the transcription of the MGMT and ANPG genes in a human hepatoma cell line (LICH cells). The two protein activities are enhanced after treatment with a variety of DNA-damaging agents. They are maximum 72 hr after the inducing treatments and remain elevated for about 120 hr. This induction is abolished when the cells are grown in the presence of protein or RNA synthesis inhibitors. Northern blot analysis shows that the DNA-damaging agents increase to different extents the transcription of the MGMT or ANPG genes. The transferase activity is also increased by DNA damage in a human glioblastoma cell line (T98G cells), but is not significantly modified in human normal fibroblasts, suggesting that this repair activity enhancement might occur preferentially in transformed cells, as we have previously shown for cells of rat origin. Therefore, these increased repair activities may play an important role in removing the lethal N3-methyladenine residues, the promutagenic O6-methylguanine lesions, and the potentially lethal chloroethyl adducts formed by the nitrosoureas used in cancer chemotherapy more efficiently from the cellular DNA.
通过检测人肝癌细胞系（LICH细胞）中O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）和N3-甲基腺嘌呤-DNA糖基化酶（ANPG）这两种DNA修复蛋白的活性以及MGMT和ANPG基因的转录情况，研究了它们的可诱导性。用多种DNA损伤剂处理后，这两种蛋白的活性增强。诱导处理后72小时活性达到最大值，并在约120小时内保持升高。当细胞在蛋白质或RNA合成抑制剂存在的情况下生长时，这种诱导作用消失。Northern印迹分析表明，DNA损伤剂不同程度地增加了MGMT或ANPG基因的转录。在人胶质母细胞瘤细胞系（T98G细胞）中，DNA损伤也增加了转移酶活性，但在人正常成纤维细胞中没有明显改变，这表明这种修复活性的增强可能优先发生在转化细胞中，正如我们之前对大鼠来源的细胞所表明的那样。因此，这些增加的修复活性可能在更有效地从细胞DNA中去除致死性的N3-甲基腺嘌呤残基、促突变的O6-甲基鸟嘌呤损伤以及癌症化疗中使用的亚硝基脲形成的潜在致死性氯乙基加合物方面发挥重要作用。
