摘要目的 观察砷暴露人群外周血白细胞组蛋白H2AK119泛素化(H2AK119 ubiquitination,H2AK119ub)和H2BK120泛素化(H2BK120ub)修饰水平,分析砷暴露与组蛋白H2AK119ub、H2BK120ub水平的关系.方法 以山西省和吉林省饮水型地方性砷中毒典型病区为调查地点,选择饮水年限为10年及以上的281名当地常住居民作为调查对象.将受检人群按照饮水砷含量分为对照组(水砷含量＜ 0.01 mg/L)、低水砷暴露组(水砷含量范围为0.01 ～ 0.05 mg/L)、中水砷暴露组(水砷含量范围为＞0.05～0.10 mg/L)、高水砷暴露组(水砷含量＞0.10mg/L).其中对照组60人(男性20人、女性40人),低水砷暴露组61人(男性27人、女性34人),中水砷暴露组50人(男性17人、女性33人),高水砷暴露组110人(男性40人、女性70人).采集受检人群所饮用的水样和即时尿样,采用原子荧光法检测水砷和尿砷含量;同时,采集外周静脉血并提取白细胞组蛋白,采用斑点杂交法检测组蛋白H2AK119ub和H2BK120ub水平.水砷、尿砷、水砷累积暴露量、H2AK119ub、H2BK120ub水平以中位数和四分位数[M(P25,P75)]表示.结果 对照组,低、中、高水砷暴露组研究对象的年龄、体质指数(body mass index,BMI)、性别、吸烟、饮酒情况比较,差异无统计学意义(x2=3.780、3.572、1.938、4.937、6.025,P均＞0.05).对照组,低、中、高水砷暴露组水砷含量[0.005(0.003,0.006)、0.024(0.017,0.037)、0.076(0.057,0.084)、0.150(0.124,0.185)mg/L]、尿砷含量[0.011(0.006,0.017)、0.018 (0.004,0.072)、0.061(0.032,0.124)、0.134(0.069,0.223)mg/L]、水砷累积暴露量[0.342 (0.248,0.477)、1.641 (1.012,2.324)、5.273 (3.690,7.036)、7.716(5.608,12.053)mg]比较,差异有统计学差异(Hc=256.041、88.615、218.610,P均＜0.01).对照组,低、中、高水砷暴露组人群外周血白细胞中H2AK119ub[1.231 (0.856,1.817)、1.244 (0.792,1.884)、1.376(0.743,1.981)、1.390 (0.906,2.045)]、H2BK120ub [0.350 (0.186,0.589)、0.363 (0.152,0.678)、0.428 (0.134,0.788)、0.276 (0.146,0.453)]水平比较,差异无统计学意义(Hc=2.130、4.330,P均＞0.05).H2AK119ub水平与水砷含量、水砷累计暴露量均无相关性(r=0.104、-0.008,P均＞0.05),与尿砷含量呈正相关(r=0.166,P＜0.05).H2BK120ub水平与水砷含量、水砷累积暴露量均呈负相关(r=-0.183、-0.159,P均＜0.05),与尿砷含量无相关性(r=-0.101,P＞0.05).H2AK 119ub水平与H2BK120ub水平呈负相关(r=-0.127,P＜0.05).结论 砷外暴露可能改变人群外周血白细胞中H2BK120ub水平.

abstractsObjective To detect the modification levels of H2AKll9 ubiquitination (H2AK119ub) and H2BK120ub,and to analyze the relationship between the levels of H2AK119ub,H2BK120ub and arsenic exposure.Methods A cross-sectional study was conducted in typical areas of drinking water type of endemic arsenicosis in Shanxi and Jilin provinces.Totally 281 residents who had drank local water for more 10 years were enrolled in this study,these participants were divided into control group (water arsenic content ＜ 0.01 mg/L),low arsenic exposure group (water arsenic content ranged 0.01-0.05 mg/L),medium arsenic exposure group (water arsenic content ranged ＞ 0.05-0.10 mg/L) and high arsenic exposure group (water arsenic content ＞ 0.10 mg/L).Among them,including 60 subjects in control group (20 males and 40 females),61 subjects in low arsenic exposure group (27 males and 34 females),50 subjects in medium arsenic exposure group (17 males and 33 females),and 110 subjects in high arsenic exposure group (40 males and 70 females).Drinking water and urine samples were collected and the arsenic content was detected by the method of atomic fluorescence spectrometry.After extracting leukocytes histone from the peripheral venous blood that collected from the subjects,the levels of H2AK119ub and H2BK120ub were detected by dot blotting.The levels of water arsenic,urinary arsenic,water arsenic accumulative intake,H2AK119ub and H2BK120ub were expressed as medium and quartile [M (P25,P75)].Results Age,body mass index (BMI),gender,smoking and alcohol drinking between control group and water arsenic exposure groups had no statistical differences (x2 =3.780,3.572,1.938,4.937,6.025,all P ＞ 0.05).Compared the contents of water arsenic [0.005 (0.003,0.006),0.024 (0.017,0.037),0.076 (0.057,0.084),0.150 (0.124,0.185) mg/L],the contents of urinary arsenic [0.011 (0.006,0.017),0.018 (0.004,0.072),0.061 (0.032,0.124),0.134 (0.069,0.223) mg/L],the water arsenic accumulative intake [0.342 (0.248,0.477),1.641 (1.012,2.324),5.273 (3.690,7.036),7.716 (5.608,12.053) mg] among the control,low,medium and high arsenic exposure groups,the differences were statistically significant (Hc =256.041,88.615,218.610,all P ＜ 0.01).Compared the levels of H2AK119ub [1.231 (0.856,1.817),1.244 (0.792,1.884),1.376 (0.743,1.981),1.390 (0.906,2.045)],H2BK120ub [0.350 (0.186,0.589),0.363 (0.152,0.678),0.428 (0.134,0.788),0.276 (0.146,0.453)] in human peripheral blood leukocytes among control,low,medium and high arsenic exposuregroups,the differences were not statistically significant (Hc =2.130,4.330,all P ＞ 0.05).There were no correlations between H2AK119ub and water arsenic content,water arsenic accumulative intake (r =0.104,-0.008,all P ＞ 0.05);there was a positive correlation between H2AK119ub and urinary arsenic content (r =0.166,P ＜ 0.05).There were negative correlations between H2BK120ub and water arsenic content,water arsenic accumulative intake (r =-0.183,-0.159,all P ＜ 0.05);there was no correlation between H2BK120ub and urinary arsenic content (r =-0.101,P ＞ 0.05).There was a negative correlation between H2AK119ub and H2BK120ub (r =-0.127,P ＜ 0.05).Conclusion External exposure to arsenic may change the levels of H2BK120ub in human peripheral blood leukocytes.