Analysis of mixture toxicity for dual combinations of heavy metals and herbicides using toxicogenomic approach

使用毒物基因组学方法分析重金属和除草剂双重组合的混合物毒性

• 批准号: 20360235
• 负责人: OKABE Satoshi
• 金额: $ 11.9万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20360235/
• 关键词: 複合毒性評価; DNAマイクロアレイ; 重金属; 農薬; HepG2細胞

The single chemical cytotoxicity showed that heavy metals and silver nanoparticles had high toxicity, respectively, but herbicides had relatively low toxicity. In contrast, the dual combinations cytotoxicity showed that the combination of silver nanoparticles and heavy metals tended to be much more toxic than silver nanoparticles or heavy metals alone, excluding the combination of silver nanoparticles and chromium (AgNPs-Cr). However, the toxicity of the combination of herbicides and heavy metals was similar to that of herbicides exposure alone. From cytotoxicity results, 5 μM of silver nanoparticles, 2.6 μM of cadmium, 7μM of arsenic and 1.1 μM of chromium were used for the DNA microarray analyses to further elucidate the mechanisms of mixture toxicity. The treatments with AgNPs-Cd (70% cytoviability), AgNPs-As (100% cytoviability) and AgNPs-Cr (140% cytoviability) altered the expression levels of 107 genes, 500 genes and 196 genes, respectively. There was a significant difference between 2 combinations (AgNPs-Cr and AgNPs-Cd) and silver nanoparticles alone on DNA replication genes such as MCM2, MCM5, MCM6, and GINS2 that are important for DNA replication fork. Furthermore, FABP1 gene was down regulated 41-fold by AgNPs-As combination. FABPs play an important role in the transport of lipids to specific compartments in the cell. In conclusion, toxicogenomic approach could elucidate synergistic toxicity by AgNPs and heavy metals, which clearly demonstrate the possible use of DNA microarray analysis for evaluation of mixture toxicity.

单一化学细胞毒性表明，重金属和纳米银分别具有较高的毒性，而除草剂的毒性相对较低；相反，双重组合细胞毒性表明，纳米银和重金属的组合往往比纳米银的毒性大得多。或单独的重金属，不包括银纳米粒子和铬的组合（AgNPs-Cr）。然而，除草剂和重金属的组合的毒性与相似。根据细胞毒性结果，使用 5 μM 银纳米颗粒、2.6 μM 镉、7 μM 砷和 1.1 μM 铬进行 DNA 微阵列分析，以进一步阐明 AgNP 混合物的毒性机制。 - Cd（70% 细胞活力）、AgNPs-As（100% 细胞活力）和 AgNPs-Cr （140% 细胞活力）分别改变了 107 个基因、500 个基因和 196 个基因的表达水平。 2 种组合（AgNPs-Cr 和 AgNPs-Cd）与单独的银纳米颗粒在 DNA 复制基因（如 MCM2）上存在显着差异。对于 DNA 复制叉很重要的 MCM5、MCM6 和 GINS2 此外，FABP1 基因下调了 41 倍。 AgNPs-As 组合在脂质转运至细胞中的特定区室中发挥重要作用。 总之，毒理学方法可以阐明 AgNPs 和重金属的协同毒性，这清楚地证明了 DNA 微阵列分析用于评估的可能性。混合物毒性。

项目成果

ヒトDNAマイクロアレイを用いた濃度依存的ヒ素毒性の評価

使用人类 DNA 微阵列评估浓度依赖性砷毒性

• 发表时间: 2009
• 作者: 多賀哲平;川田耕司;岡部聡
• 通讯作者: 岡部聡