The association between histone modification of H3K14ac and genetic damage in peripheral blood lymphocyte of coal-burning arsenicosis residents / 中华地方病学杂志

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 subgroupsmild 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 H3K14acThe 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-burningThe 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 arsenicosisBased 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 (MN1.17 ± 0.97,Wald =14.121;CA6.29 ± 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 damageThe 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 (MNβ =0.10,P ＞ 0.05;8-OHdGβ=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.