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比较8-羟基脱氧鸟苷、染色体畸变和微核技术用于评估汞化合物对人血淋巴细胞的遗传毒性。

A comparison of the 8-hydroxydeoxyguanosine, chromosome aberrations and micronucleus techniques for the assessment of the genotoxicity of mercury compounds in human blood lymphocytes.

作者信息

Ogura H, Takeuchi T, Morimoto K

机构信息

Department of Hygiene and Preventive Medicine, Osaka University School of Medicine, Japan.

出版信息

Mutat Res. 1996 Jun;340(2-3):175-82. doi: 10.1016/s0165-1110(96)90047-0.

Abstract

We compared the mechanism of action of micronuclei (MN), unstable chromosome aberrations, and 8-hydroxydeoxyguanosine (8-OHdG) levels to evaluate the genotoxicity of methyl mercuric chloride (CH3HgCl) and mercuric chloride (HgCl2) in human peripheral lymphocytes. The chromosome aberrations in human peripheral lymphocytes exposed to various concentrations of CH3HgCl or HgCl2 increased in a concentration-dependent manner and were significantly higher than the control when the cells were incubated with 1 x 10(-5) M (HgCl2) or 2 x 10(-6) M (CH3HgCl). The increase in the incidence of micronucleated lymphocytes was significant among the exposed groups, being 2 x 10(-5) M (HgCl2) and 5 x 10(-6) M (CH3HgCl) compared with the control. CH3HgCl was about 4-fold more potent than HgCl2. We determined the 8-OHdG levels in human peripheral blood mononuclear cells(PBMC) and found that they were significantly higher in the exposed groups at 1 x 10(-5) M (HgCl2) and 5 x 10(-6) M (CH3HgCl) compared with the control. A detectable (p < 0.05) increase in the level of 8-OHdG was induced by CH3HgCl at a concentration that was about 50% of the amount of HgCl2 required to produce a similar response. The data confirmed the value of the MN and/or chromosome aberration assays for assessing of HgCl2- and/or CH3HgCl-induced genotoxicity, and indicated that they are about the same concentration as the 8-OHdG assay. The presence of genotoxic effects in peripheral blood lymphocytes exposed to the mercuric compounds indicated by the chromosome aberrations and the MN assays could be partly due either to the disturbance of the spindle mechanism, or to the elevated level of 8-OHdG brought by the generation of reactive oxygen species.

摘要

我们比较了微核(MN)、不稳定染色体畸变的作用机制以及8-羟基脱氧鸟苷(8-OHdG)水平,以评估甲基汞(CH3HgCl)和氯化汞(HgCl2)对人外周血淋巴细胞的遗传毒性。暴露于不同浓度CH3HgCl或HgCl2的人外周血淋巴细胞中的染色体畸变呈浓度依赖性增加,当细胞与1×10(-5) M(HgCl2)或2×10(-6) M(CH3HgCl)孵育时,显著高于对照组。暴露组中微核淋巴细胞发生率的增加具有显著性,与对照组相比,分别为2×10(-5) M(HgCl2)和5×10(-6) M(CH3HgCl)。CH3HgCl的效力约为HgCl2的4倍。我们测定了人外周血单个核细胞(PBMC)中的8-OHdG水平,发现与对照组相比,在1×10(-5) M(HgCl2)和5×10(-6) M(CH3HgCl)时暴露组的水平显著更高。CH3HgCl在产生类似反应所需HgCl2量的约50%浓度下诱导了8-OHdG水平的可检测(p < 0.05)增加。数据证实了MN和/或染色体畸变试验在评估HgCl2和/或CH3HgCl诱导的遗传毒性方面的价值,并表明它们与8-OHdG试验的浓度大致相同。染色体畸变和MN试验表明,暴露于汞化合物的外周血淋巴细胞中存在遗传毒性效应,这可能部分归因于纺锤体机制的紊乱,或活性氧产生导致的8-OHdG水平升高。

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