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焦炉工人热休克蛋白70基因多态性与外周血淋巴细胞DNA损伤的关系

Association between heat-shock protein 70 gene polymorphisms and DNA damage in peripheral blood lymphocytes among coke-oven workers.

作者信息

Yang X, Yuan J, Sun J, Wang H, Liang H, Bai Y, Guo L, Tan H, Yang M, Wang J, Su J, Chen Y, Tanguay R M, Wu T

机构信息

Institute of Occupational Medicine and Ministry of Education Key Lab for Environment and Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.

出版信息

Mutat Res. 2008 Jan 8;649(1-2):221-9. doi: 10.1016/j.mrgentox.2007.09.004. Epub 2007 Sep 29.

Abstract

Hsp70 has been shown to act as a chaperone and be associated with cytoprotection against DNA damage caused by environmental stresses. However, it is unknown whether genetic variation in HSP70 plays a role in stress tolerance and cytoprotection against DNA damage. We determined the frequencies of three polymorphisms, HSP70-1 G190C, HSP70-2 G1267A, and HSP70-hom T2437C from 251 steel-plant workers exposed to coke-oven emission and 130 controls. We estimated the association between the HSP70variants/haplotypes and the levels of DNA damage in their peripheral blood lymphocytes detected by single-cell gel electrophoresis assay. Our results showed that overall coke-oven workers had higher levels of the Olive tail moment (Olive TM) (1.27+/-1.12) than that of the controls (0.56+/-0.99, P<0.001). Coke-oven workers with the HSP70-1 C/C genotype had higher levels of Olive TM (2.19+/-0.65), compared with HSP70-1 G/C and G/G carriers (Olive TM=1.34+/-1.09 and 1.14+/-1.08, respectively, P=0.022 and 0.003, respectively). However, the HSP70-2 G1267A and HSP70-hom T2437C polymorphisms were not associated with the levels of Olive TM (P=0.929 and 0.795, respectively). Haplotype analysis showed that carriers of TCG/TCG haplotype pairs had the highest levels of Olive TM among both the exposed subjects (2.04+/-0.59) and the controls (0.81+/-0.59). Our results suggest that the individuals with the homozygous HSP70-1 C/C genotype among the coke-oven workers may be susceptible to DNA damage.

摘要

热休克蛋白70(Hsp70)已被证明可作为一种伴侣蛋白,并与针对环境应激所致DNA损伤的细胞保护作用相关。然而,HSP70基因变异是否在应激耐受性及针对DNA损伤的细胞保护中发挥作用尚不清楚。我们测定了251名暴露于焦炉排放物的钢铁厂工人和130名对照者中三种多态性,即HSP70 - 1 G190C、HSP70 - 2 G1267A和HSP70 - hom T2437C的频率。我们通过单细胞凝胶电泳分析估计了HSP70变异体/单倍型与外周血淋巴细胞中DNA损伤水平之间的关联。我们的结果显示,总体而言,焦炉工人的橄榄尾矩(Olive TM)水平(1.27±1.12)高于对照者(0.56±0.99,P<0.001)。与HSP70 - 1 G/C和G/G携带者相比,具有HSP70 - 1 C/C基因型的焦炉工人的Olive TM水平更高(分别为2.19±0.65,而HSP70 - 1 G/C和G/G携带者的Olive TM分别为1.34±1.09和1.14±1.08,P分别为0.022和0.003)。然而,HSP70 - 2 G1267A和HSP70 - hom T2437C多态性与Olive TM水平无关(P分别为0.929和0.795)。单倍型分析显示,TCG/TCG单倍型对的携带者在暴露组(2.04±0.59)和对照组(0.81±0.59)中Olive TM水平最高。我们的结果表明,焦炉工人中具有纯合HSP70 - 1 C/C基因型的个体可能易受DNA损伤。

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