摘要
目的通过对外周血淋巴细胞DNA损伤程度和人8-羟基鸟嘌呤DNA糖苷酶（human 8-oxoguanine DNA glycosydase，hOGG1）基因多态性的研究，了解石棉肺与DNA损伤和hOGG1基因型的关系。方法以101名石棉作业工人作为观察组、141名非石棉作业工人作为对照组进行了流行病学调查。利用彗星试验检测DNA损伤程度；用多聚酶链反应邛艮制性片段长度多态性（polymerase chain reaction-restricted fragments length polymorphism，PCR-RELP）法确定hOGG1基因Ser326Cys多态分布。结果（1）石棉接触组基础DNA损伤程度（basal DNA damage，DB，34．8±16．8）、H2O2诱导后的DNA损伤程度（H2O2-induced DNA damage，DH，136．7±36．0）及修复损伤4h后的DNA损伤程度（repair DNA damage，DR，51．0±18．7）均显著高于对照组（P〈0．01）。石棉肺组DH（147．0±30．8）和DR（56．9±21．4）显著高于非石棉肺组（125．7±38．2和44．9±15．4）（P〈0．01）。（2）石棉接触组和对照组hOGG1基因Ser326Cys多态分布差异没有统计学意义（χ^2=0．22，P=0．89）。而石棉接触组中，石棉肺人群Ser／Ser、Ser／Cys、Cys／Cys基因型分布频率分别为25．5％、51．0％和23．5％，与非石棉肺人群（48．0％、36．0％和16．0％）间差异有统计学意义（χ^2=6．023，P〈0．05）。石棉肺组中Ser／Cys和Cys／Cys基因型人群，DH和DR均高于非石棉肺组相应人群（P〈0．05）。（3）在校正了年龄、性别、吸烟和饮酒等因素后，hOGG1基因型对患石棉肺的风险无明显影响（OR=0．66；95％CI=0．38～1．13）。结论接触石棉会导致DNA损伤，携带Cys等位基因的人群DNA对H2O2氧化损伤敏感性增强且DNA损伤的修复能力降低可能是促成石棉肺的原因之一。
Objective To explore the relation of asbestosis to human 8-oxoguanine DNA glycosydase （hOGG1） genotype and DNA damage, the investigation of hOGG1 polymorphism distribution and DNA strand breakages in peripheral lymphocytes was carried on in occupational population. Methods A total 101 asbestos-exposed workers and 141 controls were investigated. The DNA damage level was obtained by single cell gel electrophoresis （SCGE） and hOGG1 Ser326Cys polymorphism by PCR-RELP. Results （1） A significant increase in the exposed group was observed in comet scores at basal （34.8±16.8）, H2O2-induced （136.7±36.0） and 4 hours after repair （51.0±18.7） as compared with the control group （P 〈 0.01）. And the scores in H2O2-induced （147.0±30.8） and 4 hours after repair （56.9±21.4） were significantly higher in asbestosis workers than in non-asbestosis ones （125.7±38.2 and 44.9±15.4, P 〈 0.01）. （2）There was no differences of the genotype distribution between the asbestos group and the control group （χ^2 = 0.22, P = 0.89）. A significant difference in the distribution of this polymorphism （Ser/Ser, Ser/Cys, Cys/Cys） between asbestosis group （25.5%, 51.0%, 23.5%） and the non-asbestosis group （48.0%, 36.0%, 16.0%） was observed （χ^2 = 6.023, P 〈 0.05）. The comet scores at H2O2-induced and 4 hours after repair were higher in asbestosis subjects than in non-asbestosis ones （P 〈 0.05）. （3） After adjusting ages, sex, smoking and drinking status, the odds ratios of the Cys allele for asbestosis were 0.66 （95% CI = 0.38 - 1.13） in the exposed subjects. Conclusion The results suggested that the asbestos occupational exposure might induce DNA damage and the augment on susceptivity of H2O2 oxidation and the fall of the capacity of repairing DNA damage might be one of the mechanisms to induce asbestosis among subjects with the Cys allele.
出处
《中华预防医学杂志》
CAS
CSCD
北大核心
2006年第6期381-385,共5页
Chinese Journal of Preventive Medicine
基金
国家自然科学基金资助项目(30100147)
