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


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.


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 NaAsO2treatment.


CONCLUSIONS
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.
a The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education Department of Toxicology , School of Public Health, Guizhou Medical University , Guiyang , China.
Aihua
A
Zhang
b Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment , School of Public Health, Sun Yat-Sen University , Guangzhou , China.
Huiyao
H
Li
a The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education Department of Toxicology , School of Public Health, Guizhou Medical University , Guiyang , China.
Yun
Y
Xiao
b Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment , School of Public Health, Sun Yat-Sen University , Guangzhou , China.
Liping
L
Chen
c Department of Toxicology, School of Public Health , Guilin Medical University , Guilin , China.
Xiaonian
X
Zhu
a The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education Department of Toxicology , School of Public Health, Guizhou Medical University , Guiyang , China.
Jun
J
Li
a The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education Department of Toxicology , School of Public Health, Guizhou Medical University , Guiyang , China.
Lu
L
Ma
a The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education Department of Toxicology , School of Public Health, Guizhou Medical University , Guiyang , China.
Xueli
X
Pan
b Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment , School of Public Health, Sun Yat-Sen University , Guangzhou , China.
Wen
W
Chen
b Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment , School of Public Health, Sun Yat-Sen University , Guangzhou , China.
Zhini
Z
He
D000328:Adult; D020261:Arsenic Poisoning / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced / Q000473:pathology; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
D004268:DNA-Binding Proteins; C086984:XPC protein, human; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
DNA methylation; ERCC1; ERCC2; XPC; arsenic exposure; biomarkers