Role of H4K20me1 and base excision repair-related genes in repairing DNA damage induced by arsenic pollution through coal burning / 中华地方病学杂志

ABSTRACT

Objective To investigate the global level of histone 4 lysine 20 monomethylation (H4K20me1) and expression of base excision repair related mRNA in coal-burning-borne endemic arsenism patients and to analyze its relationship with DNA damage,in order to provide a scientific basis in deepening the interpretation of the role of arsenic in inhibiting repair of DNA damage.Methods In 2014,47 hair samples,blood samples and skin tissue samples of the cases in Xingren County Guizhou Province were collected from the voluntary surgical treatment patients with endemic arsenism (15 general pathological change cases,14 precancerous cases and 18 cancerous cases) and 12 controls.The hair arsenic content was tested via the inductively coupled plasma-mass spectrometry method.The expression of histone H4K20me1 in skin tissues was detected via the immunohistochemistry method;quantitative real-time polymerase chain reaction was used to detect the mRNA levels of poly (ADP-ribose) polymerase (PARP1),N-methylation of purine-DNA-glycosylation (MPG) and X-ray repair cross complementary gene 1 (XRCC1);and DNA damage in peripheral blood was detected by single cell gel electrophoresis test,the level of H4K20me1 in peripheral blood cells was detected by using a sandwich enzyme-linked immunosorbent assay.Results Compared with the control group [median (25 ～ 75 percentile)0.15 (0.07-0.23) μg/L],the hair arsenic content in the case group [0.34 (0.17-0.51) μg/L] was significantly increased (Z =6.037,P ＜ 0.05).Compared with the control group (0.32 ± 0.13,0.17 ± 0.12),the modification level of H4K20me1 in peripheral blood with cancerous group (0.62 ± 0.11) was significantly increased,the modification levels of H4K20me1 (0.54 ± 0.20,0.83 ± 0.10) in skin tissues were increased in the precancerous group and cancerous group (P ＜ 0.05).Compared with the control group [0.95 (0.50-1.49),1.12 (0.98-1.48),0.96 (0.67-1.17)],the mRNA expression levels of PARP1 and MPG in cancerous group [0.37 (0.30-0.44),0.38 (0.15-0.48)] were significantly decreased;the mRNA expression levels of XRCC1 [0.48 (0.38-0.89),0.32 (0.20-0.55)] were significantly decreased in the precancerous group and cancerous group (P ＜ 0.05).Compared with the control group (1.19 ± 0.55,1.27 ± 0.51),Tail DNA％ and Tail moment were significantly increased in the general pathological change group (6.49 ± 0.98,6.60 ± 1.11),the precancerous lesion group (11.22 ± 1.40,10.07 ± 1.11),and the cancerous group (20.38 ± 1.72,27.01 ± 1.78,P ＜ 0.05).There was a positive correlation between the degree of skin lesion and modification level of H4K20me1 in peripheral blood and skin tissues and DNA damage levels (TailDNA％,OTM,r =0.885,0.855,0.806,0.883,P ＜ 0.05).There was a positive correlation between modification level of H4K20me1 in peripheral blood and level of DNA damage (TailDNA％,OTM),the level of H4K20me1 protein expression in skin (r =0.535,0.804,0.754,P ＜ 0.05),and a negative correlation with mRNA expression of MPG,XRCC1 and PARP1 (r =-0.563,-0.514,-0.550,P ＜ 0.05).There was a positive correlation between the modification level of H4K20me1 in skin and DNA damage levels (TailDNA％,OTM,r =0.602,0.875,P ＜ 0.05),and a negative correlation with mRNA expression of MPG,XRCC1 and PARP1 (r =-0.492,-0.502,-0.552,P ＜ 0.05).Conclusion The arsenic pollution of coal burning may affect the level of H4K20me1 modification,inhibit mRNA transcriptional expression of PARP1,MPG and XRCC1 genes related with base excision repair,which may lead to increased DNA damage and participate in the occurrence and development of arsenic poisoning skin lesions.