Smith P J, Paterson M C
Nature. 1980 Oct 23;287(5784):747-9. doi: 10.1038/287747a0.
Ataxia telangiectasia (AT) is a rare autosomal recessive disorder in man characterized by progressive loss of muscular coordination (due to neurodegeneration) and permanent dilation of the small blood vessels of the eyes and skin. AT patients also have repeated sinopulmonary infections, immune defects associated with thymus underdevelopment, and abnormal endocrine functions. Affected patients are at high risk of developing malignancy, particularly lymphomas and lymphatic leukaemias, and there are clinical indications that AT patients are hypersensitive to conventional radiotherapy administered for treatment of malignancy. Cultured diploid fibroblasts from AT donors are consistently hypersensitive to ionizing radiation, apparently due to defective enzymatic repair of radiogenic DNA damage. We have determined the survival responses and DNA repair abilities of AT cells exposed to 4-nitroquinoline-1-oxide (4NQO), a chemical carcinogen whose DNA-damaging properties partially mimic those of ionizing radiation. We report here that certain AT cell strains show hypersensitivity to inactivation by 4NQO and defective repair of 4NQO-induced adducts in DNA.
共济失调毛细血管扩张症（AT）是一种罕见的人类常染色体隐性疾病，其特征为肌肉协调性进行性丧失（由于神经退行性变）以及眼睛和皮肤小血管的永久性扩张。AT患者还会反复发生鼻窦肺部感染、与胸腺发育不全相关的免疫缺陷以及异常的内分泌功能。患病患者患恶性肿瘤的风险很高，尤其是淋巴瘤和淋巴性白血病，并且有临床迹象表明AT患者对用于治疗恶性肿瘤的传统放疗高度敏感。来自AT供体的培养二倍体成纤维细胞对电离辐射始终高度敏感，这显然是由于放射性DNA损伤的酶促修复存在缺陷。我们已经确定了暴露于4-硝基喹啉-1-氧化物（4NQO）的AT细胞的存活反应和DNA修复能力，4NQO是一种化学致癌物，其DNA损伤特性部分类似于电离辐射。我们在此报告，某些AT细胞株对4NQO失活表现出高度敏感性，并且对4NQO诱导的DNA加合物修复存在缺陷。
