Developmental VOC Exposure in Zebrafish: Toxic Mechanisms and Biomarkers

斑马鱼发育过程中 VOC 暴露：毒性机制和生物标志物

• 批准号: 10352964
• 负责人: Tracie R Baker
• 金额: $ 30.47万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-08 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10352964
• 关键词: Acute; Address; Adsorption; Adult; Advanced Development; Animal Model; Awareness; Behavioral; Behavioral Assay; Biological; Biological Assay; Biological Markers; Birth Rate; Cardiovascular system; Chemicals; Child; Chronic; Collaborations; Communities; Complex Mixtures; Congenital Abnormality; Country; Data; Data Analyses; Dermal; Development; Disease; Dose; Endocrine system; Ensure; Environmental Health; Environmental Impact; Environmental Pollution; Epigenetic Process; Evaluation; Exposure to; Generations; Genes; Genetic Markers; Genome; Goals; Health; Hepatic; Home environment; Human; Immune; Immune system; Immunologics; Impairment; Individual; Industrialization; Ingestion; Inhalation; Intervention; Kidney; Knowledge; Leadership; Life; Link; Measures; Mediating; Mission; Modeling; Molecular; Monitor; Multiple Abnormalities; Nervous system structure; Neurologic; Outcome; Pathway interactions; Phenotype; Physicians; Policy Maker; Population; Positioning Attribute; Pregnant Women; Premature Birth; Prevention; Public Health; Reproductive Health; Research; Research Project Grants; Research Proposals; Research Training; Risk; Risk Assessment; Route; Signal Recognition Particle; Source; Superfund; System; Target Populations; Techniques; Technology; Testing; Therapeutic; Toxic effect; Transport Process; United States National Institutes of Health; Water; Work; Zebrafish; adverse outcome; anthropogenesis; aquatic organism; biomarker validation; candidate marker; community engagement; contaminated seafood; environmental chemical; epigenetic marker; epigenetic regulation; evidence base; exhaust; experimental study; exposed human population; ground water; health assessment; health of the mother; immune function; immune health; improved; indoor air; innovation; interest; neurobehavioral; neurotoxicity; novel; off-gassing; placental mammal; potential biomarker; prevent; programs; reproductive; respiratory; seal; superfund site; toxicant; transcriptomics; translational impact; urban area; urban setting; vapor intrusion; volatile organic compound

Summary/Abstract: Anthropogenic Volatile Organic Compounds (VOCs) have emerged as high priority environmental contaminants due to ubiquitous urban exposure via industrial exhaust, fuel refineries, and vehicle exhaust, as well as VOC contamination at an estimated 78% of Superfund sites. Residents in urban areas are disproportionately exposed to VOCs as a result of indoor vapor intrusion, tap water, ingestion of contaminated fish, and ambient outdoor exposure. Inhalation, ingestion, and dermal adsorption from indoor and outdoor sources are routes for human exposure, and at-risk communities are often chronically exposed to complex mixtures of VOCs. Varied adverse health impacts associated with VOC exposure involve the respiratory, cardiovascular, renal, hepatic, endocrine, immune, and nervous systems. Studies also suggest that chronic, maternal VOC exposure is linked to birth defects and preterm birth. Nonetheless, these health risks remain ill-defined. The Center for Leadership in Environmental Awareness and Research (CLEAR) seeks to reduce the impacts of environmental contaminants on both public and environmental health, focusing on the alarming rate of preterm births in Detroit. Our hypothesis is that exposure to VOCs at environmentally-relevant concentrations and mixtures will impair development, immune function, and reproductive health in zebrafish, an NIH-accepted model organism. The development of innovative, high-throughput techniques will enable the CLEAR B1 team to perform novel developmental, reproductive, neurobehavioral, immune, and multigenerational bioassays to evaluate adverse phenotypic effects of exposure to six VOCs at various concentrations (Aim 1), similarly, identify effects of exposure to VOC mixtures (Aim 2), and employ molecular techniques to identify transcriptomic and epigenetic pathways, as well as rank potential biomarkers (by sensitivity), relevant to VOC exposure and specific biological effects (Aim 3). Using data from Projects E1, E2, B3, and the CEC, we will focus our experiments on environmentally-relevant VOC concentrations and mixtures found in Detroit and at known Superfund sites. The proposed research is significant because the results are expected to fill knowledge gaps in the field at basic and applied levels and have a positive translational impact by expanding the depth of our understanding regarding health impacts of individual VOCs and VOC mixtures, critical developmental windows for these adverse health impacts and biomarkers of effect, and mechanisms for environmentally-influenced, adult-onset and multigenerational disease. These results will be shared with the research training, data analysis, and chemical analysis cores to advance the development of evidence-based strategies to prevent and treat environmentally-induced disease. Ultimately, these strategies will be used by the community engagement core to enact VOC prevention and intervention measures to improve the health of mothers and children in Detroit (Figure 1).

摘要/摘要： 人为挥发性有机化合物 (VOC) 已成为高度优先的环境问题 由于工业废气、燃料精炼厂和汽车尾气在城市中无处不在而造成的污染物， 估计 78% 的超级基金场地存在 VOC 污染。城市地区的居民是 由于室内蒸汽侵入、自来水、摄入受污染的物质，不成比例地暴露于挥发性有机化合物 鱼和环境户外暴露。室内和室外的吸入、摄入和皮肤吸收 来源是人类接触的途径，高危社区往往长期接触复杂的环境 VOC 的混合物。与 VOC 暴露相关的各种不利健康影响涉及呼吸系统、 心血管、肾脏、肝脏、内分泌、免疫和神经系统。研究还表明 母亲长期接触挥发性有机化合物与出生缺陷和早产有关。尽管如此，这些健康风险 仍然不明确。环境意识与研究领导力中心 (CLEAR) 致力于 减少环境污染物对公众和环境健康的影响，重点关注 底特律的早产率惊人。我们的假设是，在与环境相关的环境中接触 VOC 浓度和混合物会损害斑马鱼的发育、免疫功能和生殖健康 NIH 认可的模式生物。创新、高通量技术的发展将使 CLEAR B1 团队开展新颖的发育、生殖、神经行为、免疫和多代研究 生物测定法评估暴露于不同浓度的六种挥发性有机化合物的不良表型影响（目标 1）， 同样，确定暴露于 VOC 混合物的影响（目标 2），并采用分子技术来确定 与 VOC 相关的转录组和表观遗传途径，以及潜在生物标志物排名（按敏感性） 暴露和特定生物效应（目标 3）。使用来自项目 E1、E2、B3 和 CEC 的数据，我们将重点关注 我们对在底特律和已知的环境相关的 VOC 浓度和混合物进行的实验 超级基金网站。拟议的研究意义重大，因为其结果有望填补知识空白 在基础和应用层面上，并通过扩大我们的深度产生积极的转化影响 了解单个 VOC 和 VOC 混合物的健康影响、关键的发展窗口 对于这些不利的健康影响和影响的生物标志物以及受环境影响的机制， 成人发病和多代疾病。这些结果将与研究培训、数据共享 分析和化学分析核心，以促进基于证据的战略的发展，以预防和 治疗环境引起的疾病。最终，这些策略将被社区参与所使用 制定VOC预防和干预措施，改善母婴健康 底特律（图 1）。