中文摘要：

目的探讨燃煤型砷中毒人群外周血淋巴细胞组蛋白H3K14乙酰化（H3K14ac）修饰水平与砷中毒及遗传损伤的关系，为燃煤型砷中毒表观遗传调控机制研究提供新线索。方法以贵州省兴仁县燃煤型砷中毒病区交乐村为调查点，在健康体检基础上选择151例砷中毒患者作为砷中毒组，并按《地方性砷中毒诊断标准》（WS／T211-2001）将其分为轻度（62例）、中度（50例）和重度（39例）3个亚组；同时选择病区78例无砷中毒症状健康者作为对照组；采集全部观察对象外周血、发样及尿样。采用微波消解结合电感耦合等离子质谱检测发样中的砷含量；酸抽提法提取观察对象外周血淋巴细胞组蛋白，并用免疫酶联吸附试验（ELISA）检测组蛋白H3K14ac修饰水平；采用遗传学方法检测外周血淋巴细胞微核（MN）率和染色体畸变（CA）率；采用固相萃取法结合串联四级杆液质联用仪检测尿8-羟基脱氧鸟苷（8-OHdG）水平。结果①观察对象砷暴露水平与燃煤型砷中毒及H3K14ac关系分析结果：砷中毒组发砷[0．27（0．15～0.39）μg／g]高于对照组[0．15（0．08～0．20）μg/g，F=10．736，P〈0．01]，且砷中毒程度与发砷水平呈正相关关系（r=0．363，P〈0．05）；H3K14ac修饰水平与发砷水平呈正相关关系（r=0．385，P〈0．05）。②H3K14ac与燃煤型砷中毒关联性分析结果：砷中毒组H3K14ac修饰水平（4．07±4．03）明显高于对照组（1．62±1．19，F=19．753，P〈0．01），且H3K14ac修饰水平的升高是砷中毒的危险因素[OR（95％CI）=1．779（1．323-2．392），P〈0．01]。③H3K14ac与砷中毒程度关系分析结果：对照组和轻、中、重度砷中毒组组间H3K14ac修饰水平比较差异有统计学意义（F=7．524，P〈0．01）；与对照组比较，轻、中、重度砷中毒组H3K14ac修饰水平（3．70±3．20、4．95±5．47、3．49±2．62）均显著升高?

英文摘要：

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 arsenieosis subjects were recruited from Jiaole Village of Xingren County, Guizhou. According to ＂National Principle for Diagnosis of Arsenicosis＂ （WS/T 211-2001 ）, the arsenieosis 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 ① The 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） txg/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）. ②he association of H3K14ac and arsenicosis induced by coal-burning： The levels of H3K14ac in arsenicosis group