Environmental effects on dermatoxicities of polycyclic aromatic hydrocarbons

环境对多环芳烃皮肤毒性的影响

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要多环芳烃的污染已成为环境健康的威胁由于它们对包括人类在内的各种生物的毒性。先前的流行病学研究表现出PAH暴露与许多急性和慢性人类疾病之间的密切关系。在过去几年中，在环境压力源的影响下，PAH的毒性变化的证据考虑到瞬息万变的环境条件，人们对修改PAH的风险更大的关注气候变化。但是，已经做出了非常有限的努力来了解环境的影响 PAH对人类健康的毒性的变化。我们研究的长期目标是了解分子由PAH化合物引起的人类炎症性皮肤疾病的机制以及环境如何因素会影响这些化合物的皮肤毒性。拟议研究的中心假设是环境对PAH化合物结构的影响会改变其对人皮肤的毒性。三必须实现具体目标才能完成假设的检验。三个特定目标包括，1）在水盐度的影响下鉴定水pa的光降解并酸化大气二氧化碳水平提高的水状况； 2）发现PAH的皮肤毒性途径在环境影响下人类角质形成细胞； 3）验证环境修饰的PAH 体内皮肤毒性途径。为了解决这些具体目标，将在这项研究。选定的PAH化合物将在不同周围的照片中降解盐度和PCO2水平。这些环境因素有望与这些化学物质。 PAH化学物质的毒性在不同的盐度和PCO2时进行了光改性将使用三维人角质形成细胞培养和角质形成细胞/成纤维细胞共同评估水平文化模型。使用3D验证角质形成细胞中推定的PAH致病途径角质形成细胞构建体与siRNA或基因过表达测定法结合基因功能分析。将使用确定途径与皮肤炎症反应之间的关系。小鼠皮肤炎症模型。作为预测毒理学的研究，本研究的方法采用生物学途径的基本知识的优势，以开发体外和基于动物的测试以预测化学暴露的不利影响，这是环境健康科学的优先级。