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葡萄牙帕纳谢拉矿区粉碎岩石粉末在体外无细胞试验中诱导 DNA 链断裂的地球化学组成控制。

Geochemical compositional controls on DNA strand breaks induced in in vitro cell-free assays by crushed rock powders from the Panasqueira mine area, Portugal.

机构信息

Department of Earth and Environmental Sciences and Williamson Research Centre for Molecular Environmental Science, University of Manchester, Williamson Building, Oxford Road, Manchester, M13 9PL, UK.

Department of Environmental Health, College of Public Health and Health Informatics, Umm Al-Qura University, Makkah, Saudi Arabia.

出版信息

Environ Geochem Health. 2021 Jul;43(7):2631-2647. doi: 10.1007/s10653-020-00653-9. Epub 2020 Jul 9.

Abstract

DNA strand breaks are a common form of DNA damage that can contribute to chromosomal instability or gene mutations. Such strand breaks may be caused by exposure to heavy metals. The aim of this study was to assess the level of DNA strand breaks caused by µm-scale solid particles of known chemical composition with elevated heavy metals/metalloids, notably arsenic, using an in vitro cell-free DNA plasmid scission assay. These samples were incubated with and without HO to see whether damage occurs directly or indirectly through the Fenton reaction. Levels of DNA damage in the absence of HO were < 10%, but in the presence of HO, all samples showed higher levels of damage ranging from 10 to 100% suggesting that damage was being incurred through the Fenton reaction. Using bivariate correlation analysis and multiple linear regression, manganese oxide (MnO), sulphur (S), copper (Cu), and zinc (Zn) concentrations in the particulates were found to be the most significant predictors of DNA damage. The mechanism of this DNA damage formation has yet to be thoroughly investigated but is hypothesised to be due to reactive oxygen species formation. Further work is required to assess the extent of contribution of reactive oxygen species to this DNA damage, but this study highlights the potential role of chemistry and/or mineralogy to the extent and/or nature of DNA damage caused by particulates.

摘要

DNA 链断裂是一种常见的 DNA 损伤形式,可导致染色体不稳定或基因突变。这种链断裂可能是由于暴露于重金属引起的。本研究旨在使用体外无细胞 DNA 质粒断裂测定法评估具有升高的重金属/类金属(特别是砷)的 µm 级固体颗粒引起的 DNA 链断裂水平。将这些样品与 HO 一起孵育和不孵育,以观察损伤是直接发生还是通过 Fenton 反应间接发生。在没有 HO 的情况下,DNA 损伤水平<10%,但在有 HO 的情况下,所有样品均显示出更高水平的损伤,范围为 10%至 100%,表明损伤是通过 Fenton 反应引起的。使用二元相关分析和多元线性回归,发现颗粒中氧化锰(MnO)、硫(S)、铜(Cu)和锌(Zn)的浓度是 DNA 损伤的最显著预测因子。这种 DNA 损伤形成的机制尚未得到彻底研究,但据推测是由于活性氧物质的形成。需要进一步的工作来评估活性氧物质对此 DNA 损伤的贡献程度,但本研究强调了化学物质和/或矿物学对颗粒引起的 DNA 损伤的程度和/或性质的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1139/8275547/2ed97a48fccb/10653_2020_653_Fig1_HTML.jpg

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