Environmental effects on dermatoxicities of polycyclic aromatic hydrocarbons

环境对多环芳烃皮肤毒性的影响

• 批准号: 9813287
• 负责人: Wei Xu
• 金额: $ 40.05万
• 依托单位: TEXAS A&M UNIVERSITY-CORPUS CHRISTI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-14 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9813287
• 关键词: 3-Dimensional; Acute; Address; Adverse effects; Affect; Agrochemicals; Animals; Area; Aromatic Polycyclic Hydrocarbons; Biological; Biological Assay; Biomedical Research; Carbon Dioxide; Cells; Chemical Exposure; Chemicals; Chronic; Coculture Techniques; Cues; Data; Databases; Dermal; Dimensions; Disease model; Education; Engineering; Environment; Environmental Health; Environmental Impact; Environmental Pollutants; Environmental Risk Factor; Exposure to; Family; Fibroblasts; Gene Expression; Genes; Genetic; Goals; Grant; Health; High Pressure Liquid Chromatography; Human; Human body; Hydroxyl Radical; Immune; Immune response; In Situ; In Vitro; Industrial fungicide; Inflammation; Inflammatory; Inflammatory Response; Knowledge; Measures; Methods; Minority-Serving Institution; Modeling; Modification; Molecular; Mus; Organic Chemicals; Organism; Pathogenesis; Pathogenicity; Pathway interactions; Phototoxicity; Poison; Pollution; Protocols documentation; Regulation; Reporting; Research; Risk; Role; Saline; Science; Skin; Skin Tissue; Small Interfering RNA; Standardization; Structure; Students; Sunlight; Techniques; Testing; Texas; Tissues; Toxic effect; Toxicology; UV Radiation Exposure; Ultraviolet Rays; Universities; Water; anthropogenesis; aqueous; atmospheric carbon dioxide; base; career; cell type; climate change; cytotoxic; cytotoxicity; environmental change; environmental stressor; epidemiology study; experience; graduate student; human disease; in vivo; in vivo Model; interest; keratinocyte; knock-down; marine organism; ocean acidification; overexpression; pollutant; pressure; response; skin disorder; three dimensional cell culture; tool; transcriptomics; undergraduate student

Project Summary The pollution of polycyclic aromatic hydrocarbons has become a threat in environmental health because of their toxicities to a variety of organisms including humans. Previous epidemiological studies demonstrated a close relationship between PAH exposures and many acute and chronic human diseases. Evidence in the toxicity changes of PAHs under effects of environmental stressors in the past few years raised a bigger concern in the risk of modified PAHs considering the fast-changing environment conditions led by climate change. However, very limited efforts have been made to understand the effects of environmental changes on PAH toxicities to human health. The long-term goal of our study is to understand the molecular mechanism of human inflammatory skin diseases caused by the PAH compounds, and how environmental factors affect the dermatoxicities of these compounds. The central hypothesis of the proposed study is that environmental impacts on structures of PAH compounds will change their toxicities to human skin. Three specific aims will have to be accomplished to complete the test of the hypothesis. The three specific aims include, 1) to identify the photodegradation of aqueous PAHs under the effects of water salinity and acidified water condition initiated by increased atmospheric CO2 level; 2) to discover the dermatoxic pathway of PAHs to human keratinocytes under the environmental impact; and 3) to verify the environment-modified PAH dermatoxic pathway in vivo. To address these specific aims, a standardized PAH protocol will be established in this study. Selected PAH compounds will be degraded under photo exposure within different surrounding salinity and pCO2 levels. These environmental factors are expected to interact with the photodegradation of these chemicals. The toxicities of the PAH chemicals with photo-modification at different salinity and pCO2 levels will be evaluated using three-dimensional human keratinocyte culture and keratinocyte/fibroblast co- culture models. A putative PAH pathogenic pathway in keratinocytes will be validated using the 3D keratinocytes constructs combined with gene functional analyses with siRNA or gene overexpression assays. The relationship between the identified pathway and the skin inflammatory responses will be investigated using a mouse skin inflammation model. As a study in predictive toxicology, the approach of this study takes advantage of the basic knowledge of biological pathways to develop in vitro and animal-based tests to predict adverse effects of chemical exposure, which is a priority component of the Environmental Health Sciences.

项目摘要 多环芳烃污染已成为环境健康的威胁 因为它们对包括人类在内的各种生物都有毒性。既往流行病学研究 表明PAH暴露与许多急性和慢性人类疾病之间存在密切关系。 在过去的几年中，多环芳烃在环境胁迫作用下的毒性变化的证据越来越多， 考虑到快速变化的环境条件， 气候变化然而，在了解环境影响方面所做的努力非常有限。 PAH对人体健康的毒性变化。我们研究的长期目标是了解 多环芳烃化合物引起的人类炎症性皮肤病的机制，以及环境 影响这些化合物的皮肤毒性的因素。这项研究的中心假设是， 环境对多环芳烃化合物结构的影响将改变其对人体皮肤的毒性。三 要完成对假设的检验，就必须实现具体的目标。三个具体目标 主要包括：1）研究了水体中多环芳烃在盐度和酸化条件下的光降解行为 大气CO2水平升高引发的水环境; 2）发现多环芳烃的皮肤毒性途径， 环境影响下的人角质形成细胞;和3）验证环境修饰的PAH 体内皮肤毒性途径。为了实现这些具体目标，将制定标准化的PAH方案， 本研究选择的多环芳烃化合物将在不同环境条件下光暴露降解 盐度和pCO 2水平预计这些环境因素会与光降解相互作用， 这些化学品。不同盐度和pCO 2条件下光改性多环芳烃化合物的毒性 水平将使用三维人角质形成细胞培养物和角质形成细胞/成纤维细胞共培养物进行评估。 文化模式将使用3D技术验证角质形成细胞中假定的PAH致病途径。 角质形成细胞构建体结合siRNA或基因过表达测定的基因功能分析。 将使用以下方法研究所鉴定的途径与皮肤炎症反应之间的关系： 小鼠皮肤炎症模型。作为一项预测毒理学研究，本研究的方法是 生物学途径的基础知识的优势，以制定体外和动物为基础的测试，以预测 化学接触的不利影响，这是环境健康科学的优先组成部分。