Objective To compare the asbestos-induced DNA damage and repair capacities of DNA damage between 104 asbestosexposed workers and 101 control workers in Qingdao City of China and to investigate the possible association between polymorphisms in codon 399 of XRCC1 and susceptibility to asbestosis. Methods DNA damage levels in peripheral blood lymphocytes were determined by comet assay, and XRCC1 genetic polymorphisms of DNA samples from 51 asbestosis cases and 53 non-asbestosis workers with a similar asbestos exposure history were analyzed by PCR/RFLP. Results The basal comet scores (3.95±2.95) were significantly higher in asbestos-exposed workers than in control workers (0.10±0.28). After 1 h H2O2 stimulation, DNA damage of lymphocytes exhibited different increases. After a 4 h repair period, the comet scores were 50.98±19.53 in asbestos-exposed workers and 18.32±12.04 in controls. The residual DNA damage (RD) was significantly greater (P〈0.01) in asbestos-exposed workers (35.62%) than in controls (27.75%). XRCC1 genetic polymorphism in 104 asbestos-exposed workers was not associated with increased risk of asbestosis. But compared with polymorphisms in the DNA repair gene XRCC1 (polymorphisms in codon 399) and the DNA damage induced by asbestos, the comet scores in asbestosis cases with Gin/Gin, Gln/Arg, and Arg/Arg were 40.26±18.94, 38.03±28.22, and 32.01±11.65, respectively, which were higher than those in non-asbestosis workers with the same genotypes (25.58±11.08, 37.08±14.74, and 29.38±10.15). There were significant differences in the comet scores between asbestosis cases and non-asbestosis workers with Gin/Gin by Student's t-test (P〈0.05 or 0.01). The comet scores were higher in asbestosis workers with Gin/Gin than in those with Arg/Arg and in non-asbestosis workers exposed to asbestos, but without statistically significant difference. Conclusions Exposure to asbestos may be related to DNA damage or the capacity of cells to repair H2O2-induced DNA damage. DN
XIAO-HONG ZHAOCUANG JIAYONG-QUAN LIUSHAO-WEI LIULEI YANYU JINNIAN LIU
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。