砷暴露致人8-羟基鸟嘌呤DNA糖苷酶1基因甲基化及DNA氧化损伤

Arsenic exposure causes human 8-hydroxyguanine DNA glycosidase 1 gene methylation and DNA oxidative damage

目的了解人8-羟基鸟嘌呤DNA糖苷酶(hOGG1)基因DNA甲基化水平和机体氧化应激及DNA氧化损伤情况与砷中毒的关系。方法以贵州省兴仁县燃煤型砷中毒病区207名砷暴露者为砷暴露组(包括病区非患者46名、砷中毒轻度46名、中度60名、重度组55名),在非砷暴露村选择64名健康村民作为对照组。采集观察对象的外周血,应用甲基化特异性PCR(MSP)法检测其hOGG1基因甲基化水平,化学法检测血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力、丙二醛(MDA)含量,尿8-羟基脱氧鸟嘌呤(8-OHdG)含量;依据甲基化状态将上述观察对象分为hOGG1基因甲基化组(34名)和hOGG1基因非甲基化组(237名),分析其hOGG1基因DNA甲基化及氧化应激与砷中毒的关系。结果病区非患者、轻、中、重度砷中毒组砷暴露者外周血中hOGG1基因甲基化阳性率分别为4.35,13.04,15.00和29.09%,其显著高于对照组人群外周血中hOGG1基因甲基化阳性率1.56%,且hOGG1基因甲基化阳性率随着砷中毒程度的加重而增加;hOGG1基因甲基化组的血清SOD〔(85±25)kU·L-1〕、GSH-Px〔(70±26)kU·L-1〕活力、尿8-OHdG含量〔(22.5±6.8)μg·L-1〕明显低于非甲基化组〔118±41,171±56和(28±6.5)μg·L-1〕,hOGG1基因甲基化组与非甲基化组血清MDA含量无显著性差异。结论砷暴露可导致人机体hOGG1基因高甲基化和氧化与抗氧化系统失衡,从而引起DNA氧化损伤,是促进砷中毒发生发展的原因之一。

OBJECTIVE To investigate DNA hypermethylation of human 8-hydroxyguanine glycosy-lase（hOGG1 ）gene and and the level of oxidative stress and DNA oxidative damage relations with arse-nic poisoning.METHODS In ende mic coal-pollution-borne arsenism area,Xinren county,Guizhou Province,according to the diagnostic criteria of ende mic arsenism（WS /T21 1 -2001 ）,207 people with＆amp;nbsp;ende mic arsenism were selected and divided into four groups（The arsenic exposure group：46 cases, mild arsenism group：46 cases,moderate arsenism group：60 cases and severe arsenism group：55 cases）.64 residents were selected as controls in a village about 12 km away fro m the ende mic arsenism area.With the informed consent principle,peripheral blood of all respondents was collected in order to analyze DNA methylation.Methylation-specific poly merase chain reaction were respectively performed to analyze hOGG1 Hypermethylation in arsenism respondents.Che mical methods were performed on the activity of super oxide dis mutase （SOD）and glutathione peroxidase （GSH-Px）,while the contents of malondialdehyde （MDA）in the blood of patients were measured,and the contents of 8-hydroxy-2′-deox-yguanine（8-OHdG）urine of patients were measured and analysed.On the basis of methylation status are divided into hOGG1 gene methylation group （34 cases）and hOGG1 gene no methylation group （237cases）.Analysis was performd on hOGG1 gene DNA methylation and the relationship between oxi-dative stress and arsenic poisoning.RESULTS The positive rates of hypermethylation of hOGG1 were associated with the degree of arsenic poisonin （co mpared with control group,χ2 =23.916,P 〈0.05, Co mpared with the Ende mic area normal group,χ2 =12.039,P 〈0.05 ）.Co mparing with negative group,SOD〔（85 ±25）kU·L -1 〕,GSH-Px〔（70 ±26）kU·L -1 〕activity and 8-OHdG 〔（22.5 ±6.8）μg·L -1 〕contents were lower〔（1 18 ±41 ）kU·L -1 ,（171 ±56）kU·L -1 ,（28.4 ±6.5）μg·L -1 ,P 〈0.05）〕in positive group.There was no significant difference between the MDA content（P〉0.05）.CONCLUSION Coal arsenic exposure can cause hOGG1 gene high methylation and oxidation and anti-oxidation system imbalance,causing DNA oxidative damage,it is one of the reasons to pro mote the develop ment of arsenic poisoning occurred.