Data regarding DNA repair perturbations in autism, which might increase the risk of malignancy, are scarce. To evaluate whether DNA repair may be disrupted in autistic children, we assessed the incidence of endogenous basal DNA strand breaks as well as the efficiency of repairing DNA damage caused by γ-ray in lymphocytes isolated from autistic and healthy children. The incidence of DNA damage and the kinetics of DNA repair were determined by comet assay, while the incidence of residual DNA damage was evaluated by structural chromosomal aberration analysis. Transcriptome profiling of 84 genes associated with DNA damage and repair-signaling pathways was performed by RT² Profiler PCR Array. The array data were confirmed by RT-PCR and western blot studies. Our data indicate that the incidence of basal oxidative DNA strand breaks in autistic children was greater than that in nonautistic controls. Lymphocytes from autistic children displayed higher susceptibility to damage by γ-irradiation and slower repair rate than those from nonautistic children. Although the total unstable chromosomal aberrations were unaffected, lymphocytes from autistic children were more susceptible to chromosomal damage caused by γ-ray than those from nonautistic children. Transcriptomic analysis revealed that several genes associated with repair were downregulated in lymphocytes from autistic individuals and in those exposed to γ-irradiation. This may explain the increased oxidative DNA damage and reduced repair rate in lymphocytes from autistic individuals. These features may be related to the possible correlation between autism and the elevated risk of cancer and may explain the role of the disruption of the DNA repair process in the pathogenesis of autism.

中文翻译：

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通过分子细胞遗传学分析和转录组分析来评估自闭症儿童的DNA修复效率。

关于自闭症中DNA修复干扰的数据可能会增加恶性肿瘤的风险，目前尚缺乏。为了评估自闭症儿童的DNA修复是否可能受到干扰，我们评估了自闭症和健康儿童淋巴细胞中内源性基础DNA链断裂的发生率以及修复由γ射线引起的DNA损伤的效率。通过彗星试验确定DNA损伤的发生率和DNA修复的动力学，而通过结构染色体畸变分析评估残留的DNA损伤的发生率。通过RT²Profiler PCR Array对与DNA损伤和修复信号通路相关的84个基因进行转录组分析。阵列数据通过RT-PCR和western blot研究证实。我们的数据表明，自闭症儿童的基础氧化DNA链断裂的发生率高于非自闭症儿童。与非自闭症儿童相比，自闭症儿童的淋巴细胞对γ射线照射的损伤敏感性更高，修复速度较慢。尽管总的不稳定染色体畸变不受影响，但是自闭症儿童的淋巴细胞比非自闭症儿童的淋巴细胞更容易受到γ射线引起的染色体损伤。转录组学分析表明，自闭症患者的淋巴细胞和接受γ射线照射的患者的淋巴细胞中与修复相关的几个基因均被下调。这可以解释自闭症个体的淋巴细胞中氧化性DNA损伤的增加和修复率的降低。