Seminar: Functional Exposomics and Mechanisms of Toxicity-Insights from Model Systems and NAMs.

IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Environmental Health Perspectives Pub Date : 2024-09-01 Epub Date: 2024-09-04 DOI:10.1289/EHP13120
Yunjia Lai, Muhammet Ay, Carolina Duarte Hospital, Gary W Miller, Souvarish Sarkar
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引用次数: 0

Abstract

Background: Significant progress has been made over the past decade in measuring the chemical components of the exposome, providing transformative population-scale frameworks in probing the etiologic link between environmental factors and disease phenotypes. While the analytical technologies continue to evolve with reams of data being generated, there is an opportunity to complement exposome-wide association studies (ExWAS) with functional analyses to advance etiologic search at organismal, cellular, and molecular levels.

Objectives: Exposomics is a transdisciplinary field aimed at enabling discovery-based analysis of the nongenetic factors that contribute to disease, including numerous environmental chemical stressors. While advances in exposure assessment are enhancing population-based discovery of exposome-wide effects and chemical exposure agents, functional screening and elucidation of biological effects of exposures represent the next logical step toward precision environmental health and medicine. In this work, we focus on the use, strategies, and prospects of alternative approaches and model systems to enhance the current human exposomics framework in biomarker search and causal understanding, spanning from bench-based nonmammalian organisms and cell culture to computational new approach methods (NAMs).

Discussion: We visit the definition of the functional exposome and exposomics and discuss a need to leverage alternative models as opposed to mammalian animals for delineating exposome-wide health effects. Under the "three Rs" principle of reduction, replacement, and refinement, model systems such as roundworms, fruit flies, zebrafish, and induced pluripotent stem cells (iPSCs) are advantageous over mammals (e.g., rodents or higher vertebrates). These models are cost-effective, and cell-specific genetic manipulations in these models are easier and faster, compared to mammalian models. Meanwhile, in silico NAMs enhance hazard identification and risk assessment in humans by bridging the translational gaps between toxicology data and etiologic inference, as represented by in vitro to in vivo extrapolation (IVIVE) and integrated approaches to testing and assessment (IATA) under the adverse outcome pathway (AOP) framework. Together, these alternatives offer a strong toolbox to support functional exposomics to study toxicity and causal mediators underpinning exposure-disease links. https://doi.org/10.1289/EHP13120.

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研讨会:功能暴露学和毒性机理--来自模型系统和 NAMs 的启示。
背景:过去十年来,在测量暴露组化学成分方面取得了重大进展,为探究环境因素与疾病表型之间的病因学联系提供了变革性的群体尺度框架。随着分析技术的不断发展以及大量数据的产生,我们有机会通过功能分析来补充全暴露体关联研究(ExWAS),从而在机体、细胞和分子水平上推进病因学研究:暴露组学是一个跨学科领域,旨在以发现为基础分析导致疾病的非遗传因素,其中包括多种环境化学胁迫因素。暴露评估的进步正在促进基于人群的全暴露效应和化学暴露因子的发现,而暴露的功能筛选和生物效应阐明则是实现精准环境健康和医学的下一个合理步骤。在这项工作中,我们将重点关注替代方法和模型系统的使用、策略和前景,以加强当前人类暴露量子学框架在生物标记物搜索和因果关系理解方面的作用,包括从基于工作台的非哺乳动物生物和细胞培养到计算新方法(NAMs):我们访问了功能性暴露体和暴露体动力学的定义,并讨论了利用替代模型(而非哺乳动物)来描述暴露体对整个健康的影响的必要性。根据减少、替代和完善的 "三R "原则,蛔虫、果蝇、斑马鱼和诱导多能干细胞(iPSCs)等模型系统比哺乳动物(如啮齿动物或高等脊椎动物)更具优势。这些模型具有成本效益,与哺乳动物模型相比,在这些模型中进行细胞特异性遗传操作更容易、更快捷。同时,体外到体内外推法(IVIVE)和不良后果途径框架下的测试和评估综合方法(IATA)弥补了毒理学数据和病因学推断之间的转化差距,从而加强了对人类的危害识别和风险评估。这些替代方法共同提供了一个强大的工具箱,支持功能性暴露生态学研究毒性和暴露-疾病联系的因果介质。https://doi.org/10.1289/EHP13120。
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来源期刊
Environmental Health Perspectives
Environmental Health Perspectives 环境科学-公共卫生、环境卫生与职业卫生
CiteScore
14.40
自引率
2.90%
发文量
388
审稿时长
6 months
期刊介绍: Environmental Health Perspectives (EHP) is a monthly peer-reviewed journal supported by the National Institute of Environmental Health Sciences, part of the National Institutes of Health under the U.S. Department of Health and Human Services. Its mission is to facilitate discussions on the connections between the environment and human health by publishing top-notch research and news. EHP ranks third in Public, Environmental, and Occupational Health, fourth in Toxicology, and fifth in Environmental Sciences.
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