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Health Effects of the Fluorinated Pollutants; PFAS on Enamel Development

氟化污染物对健康的影响；

基本信息

批准号：
10697298
负责人：
Maiko Suzuki
金额：
$ 14.86万
依托单位：
NOVA SOUTHEASTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-12 至 2025-09-14
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10697298
关键词：
Acquired Dental Fluorosis Adverse effects Affect Alcohols Ameloblasts Amelogenesis Animal Disease Models Animal Model Animals Area Attention Cell Line Cells Child Childhood Cleft Palate Collaborations Craniofacial Abnormalities DNA Damage Data Defect Deformity Dental Dental Enamel Dental caries Dentinogenesis Development Environment Environmental Epidemiology Environmental Health Environmental Pollutants Environmental Risk Factor Environmental Science Etiology Exposure to Faculty Fishes Fluorescence Fluorides Functional disorder Funding Goals Hazardous Chemicals Health Health Hazards Histologic Human Immune system Incidence Incisor Independent Scientist Award Induction of Apoptosis Industry Inhibition of Cell Proliferation Ions Knowledge Laboratory Animals Learning Light Minerals Mitochondria Modeling Molecular Molecular Biology Mouth Diseases Mus Nanostructures Odontogenesis Organism Outcome Periodontitis Phenotype Physiology Poly-fluoroalkyl substances Prevalence Preventive Productivity Research Research Personnel Research Project Grants Research Training Rodent Scanning Electron Microscopy Science Stains Structure Testing Therapeutic Time Tooth structure Toxic Environmental Substances Toxicology Training United States Water Zebrafish alcohol effect analytical method career career development craniofacial density drinking water environmental chemistry epidemiology study experience in vivo malformation malignant mouth neoplasm manufacture men&apos s group microCT mid-career faculty mouse model novel oral biology perfluorooctanoic acid pollutant prenatal reproductive skeletal tissue skills tumor

项目摘要

Dr. Suzuki’s (PI) ultimate research goal is to identify environmental factors related to craniofacial pathophysiology and develop novel preventive and therapeutic strategies for environmental factor-associated oral diseases. This career development K02 award would provide the protected time 1) to gain expertise in physical analysis of skeletal tissues, including Micro-CT, FIB-SEM and QLF, and 2) to establish collaborative relationships with experts in environmental health science field. The proposed research project aims to characterize the health effects of fluorinated pollutants PFAS (per- and polyfluoroalkyl substances or organofluorine compounds) on tooth development. PFAS are a group of man-made organofluorine compounds, including Perfluorooctanoic acid (PFOA) and PFOA precursor, Fluorotelomer alcohols (FTOHs). PFAS do not readily breakdown in the environment and are water-soluble. PFAS can be found in drinking water and living organisms, including fish, animals and humans where PFAS can build up and persist over time. Laboratory animal studies showed that PFAS can cause tumors and adverse effects on reproductivity, development and immune system. Previous studies demonstrated that FTOHs (precursor of PFOA) induced tooth malformation, including degeneration of ameloblasts in rodent incisors. However, examination of how FTOHs alter tooth phenotype (physical and histological) is limited and the molecular mechanisms of how FTOHs affect tooth development are largely unknown. Our long-term goal is to identify the molecular mechanisms of PFAS adverse effects on odontogenesis. Our overall objective here is to establish PFAS (hazardous chemical) use in an animal model and determine how FTOHs affect amelogenesis in vivo. Our central hypothesis is that FTOHs induce DNA damage and mitochondrial damage to perturb ameloblast function during tooth development that results in enamel malformation. Our hypothesis has been formulated based on our preliminary data showing that PFOA inhibited cell proliferation, induced apoptosis, DNA damage and mitochondrial damage in ameloblast-like cell (LS8 cells). The impact of the proposed research is to define the effects of PFAS on tooth development and to highlight the molecular mechanisms involved in tooth malformation. Once PFAS adverse effects are identified in tooth formation, PFAS could be considered as a possible causative factor for cryptogenic abnormalities in dentinogenesis, including Molar Incisor Hypomineralisation (MIH) of which the etiology is unknown. We plan to test our central hypothesis and accomplish our overall objective by pursuing the Specific AIM: Identify FTOH effects on enamel phenotype in a mouse model.

铃木博士（PI）的最终研究目标是确定与颅面相关的环境因素病理生理学，并制定新的预防和治疗策略，因子相关的口腔疾病。这个职业发展K 02奖将提供保护时间1）获得骨骼组织物理分析的专业知识，包括Micro-CT，FIB-SEM和 QLF，以及2）与环境健康科学专家建立合作关系领域拟议的研究项目旨在描述氟化对健康的影响，牙齿上的污染物PFAS（全氟烷基和多氟烷基物质或有机氟化合物）发展PFAS是一组人造有机氟化合物，包括全氟辛酸（PFOA）和PFOA前体，氟调聚物醇（FTOH）。PFAS做在环境中不易分解并且是水溶性的。PFAS可以在饮用水中找到水和生物体，包括鱼类、动物和人类，PFAS可以在这些地方积聚，随着时间的推移而持续。实验动物研究表明，PFAS可导致肿瘤和不良反应，对生殖、发育和免疫系统的影响。先前的研究表明， FTOHs（PFOA的前体）诱导牙齿畸形，包括成釉细胞的变性在啮齿动物的门牙上。然而，检查FTOH如何改变牙齿表型（物理和组织学）是有限的，FTOH如何影响牙齿发育的分子机制在很大程度上是未知的。我们的长期目标是确定PFAS不利的分子机制，对牙齿发育的影响。我们的总体目标是建立PFAS（危险化学品）在动物模型中使用，并确定FTOH如何影响体内釉质形成。我们的中央有一种假说认为，FTOH通过诱导DNA损伤和线粒体损伤来干扰成釉细胞在牙齿发育过程中起作用，导致釉质畸形。我们的假设是根据我们的初步数据制定，PFOA抑制细胞增殖，诱导成釉细胞样细胞（LS 8细胞）凋亡、DNA损伤和线粒体损伤。的影响提出的研究的目的是确定PFAS对牙齿发育的影响，并强调牙齿畸形的分子机制一旦PFAS的不良反应在牙齿形成中确定，PFAS可以被认为是一个可能的致病因素，牙本质发生中的隐源性异常，包括磨牙切牙矿化不足（MIH），病因不明我们计划测试我们的中心假设，并完成我们的整体目的：通过追求特定的目的：确定FTOH对小鼠牙釉质表型的影响模型