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表观遗传生物标志物作为化学危害评估工具:利用模式生物斑马鱼进行基因表达谱分析

Epigenetic biomarkers as tools for chemical hazard assessment: Gene expression profiling using the model Danio rerio.

作者信息

Torres Tiago, Ruivo Raquel, Santos Miguel Machado

机构信息

CIMAR/CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Group of Endocrine Disruptors and Emerging Contaminants, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal; FCUP - Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal.

CIMAR/CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Group of Endocrine Disruptors and Emerging Contaminants, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal.

出版信息

Sci Total Environ. 2021 Jun 15;773:144830. doi: 10.1016/j.scitotenv.2020.144830. Epub 2021 Jan 29.

DOI:10.1016/j.scitotenv.2020.144830
PMID:33592472
Abstract

Recent reports raise the concern that exposure to several environmental chemicals may induce persistent changes that go beyond the exposed organisms, being transferred to subsequent generations even in the absence of the original chemical insult. These changes in subsequent non-exposed generations have been related to epigenetic changes. Although highly relevant for hazard and risk assessment, biomarkers of epigenetic modifications that can be associated with adversity, are still not integrated into hazard assessment frameworks. Here, in order to validate new biomarkers of epigenetic modifications in a popular animal model, zebrafish embryos were exposed to different concentrations of Bisphenol A (0.01, 0.1, 1 and 10 mg/L) and Valproic Acid (0.8, 4, 20 and 100 mg/L), two chemicals reported to alter the modulation of the epigenome. Morphological abnormalities and epigenetic changes were assessed at 80 hours-post fertilization, including DNA global methylation and gene expression of both DNA and histone epigenetic modifications. Gene expression changes were detected at concentrations below those inducing morphological abnormalities. These results further support the importance of combining epigenetic biomarkers with apical endpoints to improve guidelines for chemical testing and hazard assessment, and favour the integration of new biomarkers of epigenetic modifications into the standardized OECD test guideline 236 with zebrafish embryos.

摘要

最近的报告引发了人们的担忧,即接触几种环境化学物质可能会引发持续的变化,这些变化不仅影响接触化学物质的生物体,甚至在没有原始化学物质侵害的情况下也会传递给后代。后代未接触化学物质的几代人中出现的这些变化与表观遗传变化有关。尽管表观遗传修饰的生物标志物与危害和风险评估高度相关,且可与逆境相关联,但这些生物标志物仍未纳入危害评估框架。在此,为了在一种常用的动物模型中验证表观遗传修饰的新生物标志物,将斑马鱼胚胎暴露于不同浓度的双酚A(0.01、0.1、1和10毫克/升)和丙戊酸(0.8、4、20和100毫克/升)中,这两种化学物质据报道会改变表观基因组的调控。在受精后80小时评估形态异常和表观遗传变化,包括DNA整体甲基化以及DNA和组蛋白表观遗传修饰的基因表达。在诱导形态异常的浓度以下就检测到了基因表达变化。这些结果进一步支持了将表观遗传生物标志物与顶端终点相结合以改进化学测试和危害评估指南的重要性,并有利于将表观遗传修饰的新生物标志物纳入经合组织关于斑马鱼胚胎的标准化测试指南236中。

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