{"title":"8-羟基脱氧鸟苷、染色体畸变和微核技术评估人血液淋巴细胞中汞化合物遗传毒性的比较","authors":"Hiroko Ogura, Toru Takeuchi, Kanehisa Morimoto","doi":"10.1016/S0165-1110(96)90047-0","DOIUrl":null,"url":null,"abstract":"<div><p>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 (CH<sub>3</sub>HgCl) and mercuric chloride (HgCl<sub>2</sub>) in human peripheral lymphocytes. The chromosome aberrations in human peripheral lymphocytes exposed to various concentrations of CH<sub>3</sub>HgCl or HgCl<sub>2</sub> increased in a concentration-dependent manner and were significantly higher than the control when the cells were incubated with 1 × 10<sup>−5</sup> M (HgCl<sub>2</sub>) or 2 × 10<sup>−6</sup> M (CH<sub>3</sub>HgCl). The increase in the incidence of micronucleated lymphocytes was significant among the exposed groups, being 2 × 10<sup>−5</sup> M (HgCl<sub>2</sub>) and 5 × 10<sup>−6</sup> M (CH<sub>3</sub>HgCl) compared with the control. CH<sub>3</sub>HgCl was about 4-fold more potent than HgCl<sub>2</sub>. 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 × 10<sup>−5</sup> M (HgCl<sub>2</sub>) and 5 × 10<sup>−6</sup> M (CH<sub>3</sub>HgCl) compared with the control. A detectable (<em>p</em> < 0.05) increase in the level of 8-OHdG was induced by CH<sub>3</sub>HgCl at a concentration that was about 50% of the amount of HgCl<sub>2</sub> required to produce a similar response. The data confirmed the value of the MN and/or chromosome aberration assays for assessing of HgCl<sub>2</sub>- and/or CH<sub>3</sub>HgCl-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.</p></div>","PeriodicalId":100940,"journal":{"name":"Mutation Research/Reviews in Genetic Toxicology","volume":"340 2","pages":"Pages 175-182"},"PeriodicalIF":0.0000,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1110(96)90047-0","citationCount":"78","resultStr":"{\"title\":\"A comparison of the 8-hydroxydeoxyguanosine, chromosome aberrations and micronucleus techniques for the assessment of the genotoxicity of mercury compounds in human blood lymphocytes\",\"authors\":\"Hiroko Ogura, Toru Takeuchi, Kanehisa Morimoto\",\"doi\":\"10.1016/S0165-1110(96)90047-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 (CH<sub>3</sub>HgCl) and mercuric chloride (HgCl<sub>2</sub>) in human peripheral lymphocytes. The chromosome aberrations in human peripheral lymphocytes exposed to various concentrations of CH<sub>3</sub>HgCl or HgCl<sub>2</sub> increased in a concentration-dependent manner and were significantly higher than the control when the cells were incubated with 1 × 10<sup>−5</sup> M (HgCl<sub>2</sub>) or 2 × 10<sup>−6</sup> M (CH<sub>3</sub>HgCl). The increase in the incidence of micronucleated lymphocytes was significant among the exposed groups, being 2 × 10<sup>−5</sup> M (HgCl<sub>2</sub>) and 5 × 10<sup>−6</sup> M (CH<sub>3</sub>HgCl) compared with the control. CH<sub>3</sub>HgCl was about 4-fold more potent than HgCl<sub>2</sub>. 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 × 10<sup>−5</sup> M (HgCl<sub>2</sub>) and 5 × 10<sup>−6</sup> M (CH<sub>3</sub>HgCl) compared with the control. A detectable (<em>p</em> < 0.05) increase in the level of 8-OHdG was induced by CH<sub>3</sub>HgCl at a concentration that was about 50% of the amount of HgCl<sub>2</sub> required to produce a similar response. The data confirmed the value of the MN and/or chromosome aberration assays for assessing of HgCl<sub>2</sub>- and/or CH<sub>3</sub>HgCl-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.</p></div>\",\"PeriodicalId\":100940,\"journal\":{\"name\":\"Mutation Research/Reviews in Genetic Toxicology\",\"volume\":\"340 2\",\"pages\":\"Pages 175-182\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1996-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S0165-1110(96)90047-0\",\"citationCount\":\"78\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mutation Research/Reviews in Genetic Toxicology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0165111096900470\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutation Research/Reviews in Genetic Toxicology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0165111096900470","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 78
摘要
我们比较了微核(MN)、不稳定染色体畸变和8-羟基脱氧鸟苷(8-OHdG)水平的作用机制,以评估甲基氯化汞(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的染色体畸变呈浓度依赖性增加,且在1 × 10−5 M (HgCl2)或2 × 10−6 M (CH3HgCl)中孵育的细胞显著高于对照组。与对照组相比,暴露组微核淋巴细胞的发生率显著增加,分别为2 × 10−5 M (HgCl2)和5 × 10−6 M (CH3HgCl)。CH3HgCl的效力大约是HgCl2的4倍。我们测定了人外周血单核细胞(PBMC)中的8-OHdG水平,发现在1 × 10−5 M (HgCl2)和5 × 10−6 M (CH3HgCl)暴露组中,与对照组相比,8-OHdG水平显著升高。可检测的(p <0.05),浓度约为产生类似反应所需的50%的CH3HgCl诱导8-OHdG水平升高。这些数据证实了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。外周血淋巴细胞暴露于汞化合物后出现遗传毒性效应的原因可能是由于纺锤体机制受到干扰,也可能是由于活性氧的产生导致8-OHdG水平升高。
A comparison of the 8-hydroxydeoxyguanosine, chromosome aberrations and micronucleus techniques for the assessment of the genotoxicity of mercury compounds in human blood lymphocytes
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 × 10−5 M (HgCl2) or 2 × 10−6 M (CH3HgCl). The increase in the incidence of micronucleated lymphocytes was significant among the exposed groups, being 2 × 10−5 M (HgCl2) and 5 × 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 × 10−5 M (HgCl2) and 5 × 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.