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采用彗星试验法评估被诊断为自闭症谱系障碍的儿科患者父母的DNA修复能力。

Evaluation of DNA repair capacity in parents of pediatric patients diagnosed with autism spectrum disorder using the comet assay procedure.

作者信息

Akouchekian Mansoureh, Alizadeh Rasoul, Beiranvandi Fatemeh, Dehghan Manshadi Masoumeh, Taherizadeh Fatemeh, Hakim Shooshtari Mitra

机构信息

Department of Medical Genetics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

IBRO Neurosci Rep. 2023 Oct 19;15:304-309. doi: 10.1016/j.ibneur.2023.10.003. eCollection 2023 Dec.

Abstract

BACKGROUND

Autism Spectrum Disorder (ASD) is characterized by impairments in social communication, limited repetitive behaviors, impaired language development, and interest or activity patterns, which include a group complex neurodevelopmental syndrome with diverse phenotypes that reveal considerable etiological and clinical heterogeneity and are also considered one of the most heritable disorders (over 90%). Genetic, epigenetic, and environmental factors play a role in the development of ASD.

AIM

This study was designed to investigate the extent of DNA damage in parents of autistic children by treating peripheral blood mononuclear cells (PBMCs) with bleomycin and hydrogen peroxide (H2O2).

METHODS

Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll method and treated with a specific concentration of bleomycin and H2O2 for 30 min and 5 min, respectively. Then, the degree of DNA damage was analyzed by the alkaline comet assay or single cell gel electrophoresis (SCGE), an effective way to measure DNA fragmentation in eukaryotic cells.

RESULTS

Our findings revealed that there is a significant difference in the increase of DNA damage in parents with affected children compared to the control group, which can indicate the inability of the DNA molecule repair system. Furthermore, our study showed a significant association between fathers' occupational difficulties (exposed to the influence of environmental factors), as well as family marriage, and suffering from ASD in offspring.

CONCLUSION

Our results suggested that the influence of environmental factors on parents of autistic children may affect the development of autistic disorder in their offspring. Subsequently, based on our results, investigating the effect of environmental factors on the amount of DNA damage in parents with affected children requires more studies.

摘要

背景

自闭症谱系障碍(ASD)的特征是社交沟通受损、重复行为有限、语言发展受损以及兴趣或活动模式异常,它是一组复杂的神经发育综合征,具有多样的表型,显示出相当大的病因和临床异质性,并且也被认为是遗传性最强的疾病之一(超过90%)。遗传、表观遗传和环境因素在ASD的发展中起作用。

目的

本研究旨在通过用博来霉素和过氧化氢(H2O2)处理外周血单个核细胞(PBMC)来调查自闭症儿童父母的DNA损伤程度。

方法

采用Ficoll法分离外周血单个核细胞(PBMC),分别用特定浓度的博来霉素和H2O2处理30分钟和5分钟。然后,通过碱性彗星试验或单细胞凝胶电泳(SCGE)分析DNA损伤程度,这是一种测量真核细胞中DNA片段化的有效方法。

结果

我们的研究结果显示,与对照组相比,有患病子女的父母的DNA损伤增加存在显著差异,这可能表明DNA分子修复系统存在缺陷。此外,我们的研究表明,父亲的职业困难(暴露于环境因素的影响)以及家庭婚姻与后代患ASD之间存在显著关联。

结论

我们的结果表明,环境因素对自闭症儿童父母的影响可能会影响其后代自闭症谱系障碍的发展。随后,基于我们的结果,研究环境因素对有患病子女的父母DNA损伤量的影响需要更多的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ec/10598524/5b8ef9add7fd/gr1.jpg

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