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