The association between histone modification of H3K14ac and genetic damage in peripheral blood lymphocyte of coal-burning arsenicosis residents
10.3760/cma.j.issn.2095-4255.2017.09.004
- VernacularTitle:燃煤型砷中毒人群外周血淋巴细胞组蛋白H3K14乙酰化与遗传损伤关联性研究
- Author:
Lu MA
1
;
Jun LI
;
Shaofeng WEI
;
Bing LIANG
;
Tingting XIE
;
Xilan WANG
;
Aihua ZHANG
Author Information
1. 550025贵阳,贵州医科大学环境污染与疾病监控教育部重点实验室,公共卫生学院卫生毒理学教研室
- Keywords:
Arsenicosis;
Histone modification;
H3K14ac;
Chromosomal aberrations
- From:
Chinese Journal of Endemiology
2017;36(9):639-643
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the association of H3K14 acetylation (ac) with arsenicosis induced by coal-burning and arsenic-induced genetic damage,which might help us to find an biomarker to monitor the arsenicosis and arsenic-induced toxicity.Methods Totally 151 arsenicosis subjects were recruited from Jiaole Village of Xingren County,Guizhou.According to "National Principle for Diagnosis of Arsenicosis" (WS/T 211-2001),the arsenicosis group was divided into 3 subgroups:mild poisoning (n =62),intermediate poisoning (n =50) and severe poisoning (n =39).The control group was comprised of 78 healthy villagers from Jiaole Village who were exhibited no signs of arseniasis.The hair,the urine and the peripheral blood samples were collected from the subjects.The contents of arsenic in the hair samples were analyzed with inductively coupled plasma mass spectrometry.Histones were extracted from human peripheral blood lymphocytes (PBLCs) using the method of acid extraction.The levels of H3K14ac was measured with a sandwich enzyme-linked immunosorbent assay (ELISA).The rate of micronucleus (MN) and chromosome aberration (CA) of peripheral blood lymphocytes were examined by genetic methods.The levels of urinary 8-hydroxy-2 deoxyguanosine (8-OHdG) in all the subjects were measured with the high performance liquid lhromatography-mass spectrometry (HPLC-MS).Results ①The association of arsenic-exposure with arsenicosis induced by coal-burning and H3K14ac:The levels of hair arsenic in arsenicosis group [0.27(0.15-0.39) μg/g] was significant higher than that in control group [0.15 (0.08-0.20) μg/g,F=10.736,P ＜ 0.01].The degree of arsenicosis was positive correlation with the hair-arsenic level (r =0.363,P ＜ 0.05).The levels of H3K14ac was also positive correlation with the hair-arsenic level (r =0.385,P ＜ 0.05).②The association of H3K14ac and arsenicosis induced by coal-burning:The levels of H3K14ac in arsenicosis group (4.07 ± 4.03) was 2.5-fold higher than that in control group (1.62-± 1.19,F =19.753,P ＜ 0.01).H3K14ac was a risk factor of arsenicosis,the risk of arsenicosis increased correspondingly with the levels of H3K14ac [OR (95％CI) =1.779 (1.323-2.392),P ＜ 0.01].③The correlation of H3K14ac and the degree of arsenicosis:Based on the degree of arsenicosis,we found a significant difference in the levels of H3K14ac among the four groups (F =7524,P ＜ 0.01).Compared with the non-poisoning group (1.62 ± 1.19),the levels of H3K14ac in mild poisoning,intermediate poisoning and severe poisoning subgroups (3.70 ± 3.20,4.95 ± 5.47,3.49 ± 2.62) were increased (all P ＜ 0.01),but there were no significant differences in the levels of H3K14ac between the mild poisoning,intermediate poisoning and severe poisoning subgroups (P ＞ 0.05).(④)The genetic damage of all subjects:The rate of MN (2.03 ± 1.55) and CA (12.44 ± 5.01) in arsenicosis group were significantly higher than those in control group (MN:1.17 ± 0.97,Wald =14.121;CA:6.29 ± 2.41,Wald =83.164,P ＜ 0.05).Urinary 8-OHdG was increased in arsenicosis group than that in control group [(3.80 ± 3.88),(2.33 ±1.34) μg/g Cr,F =6.116,P ＜ 0.05].⑤The association of H3K14ac with genetic damage:The results revealed that H3K14ac modification was positively correlated with the rate of CA (β =0.84,P ＜ 0.01).The level of H3K14ac was not significantly associated with the rate of MN and urinary 8-OHdG (MN:β =0.10,P ＞ 0.05;8-OHdG:β=0.05,P ＞ 0.05).Conclusions The increase of H3K14ac modification in human peripheral blood lymphocytes is a risk factor of arsenic poisoning.Additionally,the dysregulation of H3K14ac was significant association with arsenic-induced chromosomal aberrations.
