Little is known about genetic and epigenetic alterations in autism spectrum disorder. Moreover, the efficiency of DNA repair in autism must be improved to correct these alterations. We examined whether 3-aminobenzamide (3-AB) could reverse these alterations. We conducted experiments to clarify the molecular mechanism underlying these ameliorations. An assessment of genetic and epigenetic alterations by a modified comet assay showed elevated levels of oxidative DNA strand breaks and DNA hypermethylation in BTBR T⁺Itpr3^tf/J (BTBR) mice used as a model of autism. Oxidative DNA strand breaks and DNA methylation were further quantified fluorometrically, and the results showed similar changes. Conversely, 3-AB treated BTBR mice showed a significant reduction in these alterations compared with untreated mice. The expressions of 43 genes involved in DNA repair were altered in BTBR mice. RT² Profiler PCR Array revealed significantly altered expression of seven genes, which was confirmed by RT-PCR analyses. 3-AB treatment relieved these disturbances and significantly improved Ogg1 and Rad1 up-regulation. Moreover, autism-like behaviors were also mitigated in BTBR animals by 3-AB treatment without alterations in locomotor activities. The simultaneous effects of reduced DNA damage and DNA methylation levels as well as the regulation of repair gene expression indicate the potential of 3-AB as a therapeutic agent to decrease the levels of DNA damage and DNA methylation in autistic patients. The current data may help in the development of therapies that ultimately provide a better quality of life for individuals suffering from autism.

关于自闭症谱系障碍的遗传和表观遗传改变知之甚少。而且，必须提高自闭症中DNA修复的效率，以纠正这些改变。我们检查了3-氨基苯甲酰胺（3-AB）是否可以逆转这些改变。我们进行了实验，以阐明这些改善作用的分子机制。通过改进的彗星试验对遗传和表观遗传学变化的评估显示，BTBR T ⁺ Itpr3 ^tf中的氧化性DNA链断裂和DNA超甲基化水平升高/ J（BTBR）小鼠用作自闭症模型。氧化DNA链断裂和DNA甲基化进一步用荧光法定量，结果显示出相似的变化。相反，与未经治疗的小鼠相比，经3-AB处理的BTBR小鼠显示出这些改变的明显减少。在BTBR小鼠中，涉及DNA修复的43个基因的表达发生了改变。RT ² Profiler PCR Array揭示了七个基因表达的显着改变，这已通过RT-PCR分析得到证实。3-AB治疗缓解了这些干扰，并显着改善了Ogg1和Rad1上调。此外，在不改变运动活性的情况下，通过3-AB治疗在BTBR动物中也减轻了自闭症样行为。减少的DNA损伤和DNA甲基化水平以及调节修复基因表达的同时作用表明，3-AB作为治疗剂有可能降低自闭症患者的DNA损伤和DNA甲基化水平。当前数据可能有助于治疗方法的发展，从而最终为自闭症患者提供更好的生活质量。