Ataxi A-T elangiectasia (AT) is a multisystem, complex and rare disease inherited in an autosomal recessive manner. Homozygous individuals have a variety of pathological manifestations, however, heterozygotes only present a higher risk of developing cancer. We evaluated the background levels of DNA damage (basal damage) and cell response to bleomycin or ionizing radiation using Comet assay and the cytokinesis-block micronucleus (CBMN) test in individuals with AT, their parents and controls. To evaluate DNA repair, the challenge experiment with ionizing radiation was performed using Comet assay, and different recovery times were evaluated. Results showed that basal MN frequencies differ between patients, parents and controls. Meanwhile, using the Comet assay, the results from the basal analysis do not differ between the groups, but monitoring the kinetics of DNA repair, we verified that the group of patients showed a delay in repair, compared to controls. Another finding was the nuclear bud (NBUD) frequency: spontaneous and induced cell cultures (with bleomycin and radiation) showed clear differences between patients, parents and controls. The CBMN assay and repair measurement with the Comet assay can help in the diagnosis of AT patients and ATM gene carriers, as complementary methods. The use of genomic instability evaluation techniques for the identification of the heterozygotes in families, where at least one member is affected, may be of great clinical importance.

中文翻译：

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共济失调毛细血管扩张症患者及其父母的DNA损伤和修复。

共济失调AT血管扩张（AT）是一种以常染色体隐性方式遗传的多系统，复杂且罕见的疾病。纯合子个体具有多种病理学表现，但是，杂合子仅呈现出罹患癌症的更高风险。我们使用彗星分析和胞质分裂阻滞微核（CBMN）测试评估了AT，其父母和对照个体的DNA损伤（基础损伤）和细胞对博来霉素或电离辐射的反应的背景水平。为了评估DNA修复，使用Comet分析进行了电离辐射挑战实验，并评估了不同的恢复时间。结果显示，患者，父母和对照之间的基础MN频率不同。同时，使用Comet分析，两组之间基础分析的结果没有差异，但通过监测DNA修复的动力学，我们证实与对照组相比，该组患者的修复延迟。另一个发现是核芽（NBUD）频率：自发和诱导细胞培养（博来霉素和放射）显示患者，父母和对照之间存在明显差异。作为补充方法，CBMN检测和彗星检测的修复测量可以帮助诊断AT患者和ATM基因携带者。使用基因组不稳定性评估技术鉴定至少一个成员受到影响的家庭杂合子可能具有重要的临床意义。自发和诱导的细胞培养（博来霉素和放射）显示患者，父母和对照之间存在明显差异。作为补充方法，CBMN检测和彗星检测的修复测量可以帮助诊断AT患者和ATM基因携带者。使用基因组不稳定性评估技术鉴定至少一个成员受到影响的家庭杂合子可能具有重要的临床意义。自发和诱导的细胞培养（博来霉素和放射）显示患者，父母和对照之间存在明显差异。作为补充方法，CBMN检测和彗星检测的修复测量可以帮助诊断AT患者和ATM基因携带者。使用基因组不稳定性评估技术鉴定至少一个成员受到影响的家庭杂合子可能具有重要的临床意义。