Aberrant methylation of nucleotide excision repair genes is associated with chronic arsenic poisoning

核苷酸切除修复基因异常甲基化与慢性砷中毒有关

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作者:Aihua Zhang, Huiyao Li, Yun Xiao, Liping Chen, Xiaonian Zhu, Jun Li, Lu Ma, Xueli Pan, Wen Chen, Zhini He

Conclusion

Hypermethylation of ERCC1 and ERCC2 and concomitant suppression of gene expression might be served as the epigenetic marks associated with arsenic exposure and adverse health effects.

Methods

Hundred and two endemic arsenicosis patients and 36 healthy subjects were recruited. Methylight and bisulfite sequencing (BSP) assays were used to examine the methylation status of ERCC1, ERCC2 and XPC genes in peripheral blood lymphocytes (PBLs) and skin lesions of arsenicosis patients and NaAsO2-treated HaCaT cells.

Objective

To define whether aberrant methylation of DNA repair genes is associated with chronic arsenic poisoning.

Results

Hypermethylation of ERCC1 and ERCC2 and suppressed gene expression were found in PBLs and skin lesions of arsenicosis patients and was correlated with the level of arsenic exposure. Particularly, the expression of ERCC1 and ERCC2 was associated with the severity of skin lesions. In vitro studies revealed an induction of ERCC2 hypermethylation and decreased mRNA expression in response to NaAsO2 treatment.

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