Assessment of the Genotoxic Hazard of Estuarine Sediments Using an Integrative Approach With LacZ Plasmid-Based Transgenic Mice.

IF 2.3 4区 医学 Q3 ENVIRONMENTAL SCIENCES
Miguel Pinto, Joana Sacadura, Pedro M Costa, Sandra Caeiro, Henriqueta Louro, Maria J Silva
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引用次数: 0

Abstract

Under the influence of multiple anthropogenic pressures, from industrial to agricultural activities, estuaries have long been regarded as particularly sensitive ecosystems to contamination. The present study aimed at investigating the genotoxic potential of a contaminated sediment sample from an urban and industrial area of the Sado Estuary, by combining the analysis of multiple endpoints in the LacZ plasmid-based transgenic mouse model exposed for 28 days to contaminated estuarine sediment extracts through drinking water. The DNA and chromosome damaging effects were monitored in peripheral blood at 7-day intervals using the standard and enzyme-modified Comet assay, as well as the micronucleus assays in peripheral blood cells. After euthanasia, DNA damage was analyzed in several mouse tissues, and LacZ mutant frequencies were determined in the liver. Livers were also surveyed for histopathological analysis. A time-dependent increase in micronuclei frequency was seen at all tested doses, in spite of no induction of DNA damage in any organ or mutation induction in the liver of exposed mice. The liver from mice exposed to sediment extracts did not reveal major alterations besides evidence of inflammation. Overall, the integration of the endpoints analyzed in the mice is suggestive of potential chronic, rather than acute, adverse effects in vivo, and points to the need for further research in the resident human population in the area. This experimental design can be used to assess the genotoxicity of complex environmental mixtures, understand how they work, and reduce costs and resources while speeding up data collection and interpretation.

利用LacZ质粒转基因小鼠综合评价河口沉积物的遗传毒性危害。
在工业和农业活动等多种人为压力的影响下,河口一直被视为对污染特别敏感的生态系统。本研究旨在通过结合LacZ质粒转基因小鼠模型的多个终点分析,研究来自佐渡河口城市和工业区的污染沉积物样本的遗传毒性潜力,该模型通过饮用水暴露于受污染的河口沉积物提取物28天。使用标准和酶修饰的Comet试验以及外周血细胞微核试验,每隔7天监测外周血中的DNA和染色体损伤效应。在安乐死后,分析了几个小鼠组织中的DNA损伤,并确定了肝脏中LacZ突变频率。肝脏也进行了组织病理学分析。在所有测试剂量下,微核频率都随时间增加,尽管没有在任何器官中诱导DNA损伤或在暴露小鼠的肝脏中诱导突变。小鼠的肝脏暴露于沉积物提取物中,除了炎症证据外,没有显示出重大变化。总体而言,在小鼠中分析的终点的整合提示了体内潜在的慢性而非急性不良反应,并指出需要在该地区的常住人口中进行进一步研究。该实验设计可用于评估复杂环境混合物的遗传毒性,了解其工作原理,并在加快数据收集和解释的同时降低成本和资源。
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来源期刊
CiteScore
5.40
自引率
10.70%
发文量
52
审稿时长
12-24 weeks
期刊介绍: Environmental and Molecular Mutagenesis publishes original research manuscripts, reviews and commentaries on topics related to six general areas, with an emphasis on subject matter most suited for the readership of EMM as outlined below. The journal is intended for investigators in fields such as molecular biology, biochemistry, microbiology, genetics and epigenetics, genomics and epigenomics, cancer research, neurobiology, heritable mutation, radiation biology, toxicology, and molecular & environmental epidemiology.
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