Antonelli A, Elli R, Marcucci L, Bosi R, Kobal D, Petrinelli P
Dipartimento di Biopatologia Umana, Università La Sapienza, Rome, Italy.
Mutat Res. 1991 Jul;255(1):11-8. doi: 10.1016/0921-8777(91)90013-f.
Ataxia telangiectasia (AT) cells are known to be hypersensitive to ionizing radiations and to drugs such as bleomycin and epipodophyllotoxin VP16, a topoisomerase II poison. Both of these produce DNA double-strand breaks even if through different mechanisms. In this work we analyzed the sensitivity to bleomycin and to epipodophyllotoxin of AT cells after transfection with pR plasmid. This plasmid, interacting with bacterial SOS repair pathways, expresses itself in mammalian cells conferring cell resistance to the SOS inducers UV and 4NQO and cell sensitivity to different drugs such as bleomycin. This effect is presumably due to the interaction of pR products with double-strand breaks. Our findings indicate that pR plasmid, in both AT lines tested (AT5BIVA fibroblasts and ATL6 lymphoblasts), expresses itself (increasing UV protection) and amplifies the already enhanced AT cell sensitivity to both bleomycin and VP16.
共济失调毛细血管扩张症（AT）细胞对电离辐射以及诸如博来霉素和鬼臼毒素VP16（一种拓扑异构酶II毒药）等药物高度敏感。这两种物质都会导致DNA双链断裂，尽管其机制不同。在这项研究中，我们分析了用pR质粒转染后的AT细胞对博来霉素和鬼臼毒素的敏感性。该质粒与细菌的SOS修复途径相互作用，在哺乳动物细胞中表达，赋予细胞对SOS诱导剂紫外线和4NQO的抗性以及对不同药物（如博来霉素）的敏感性。这种效应可能是由于pR产物与双链断裂的相互作用。我们的研究结果表明，在所测试的两种AT细胞系（AT5BIVA成纤维细胞和ATL6淋巴细胞）中，pR质粒都能表达（增强对紫外线的保护作用），并放大了AT细胞对博来霉素和VP16已有的增强敏感性。
