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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：
10371715
负责人：
Maiko Suzuki
金额：
$ 7.31万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-15 至 2023-03-23
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10371715
关键词：
Acquired Dental Fluorosis Adverse effects Affect Alcohols Ameloblasts Amelogenesis Animal Disease Models Animal Model Animals Apoptosis Area Attention Cell Line Cell Proliferation 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 Immune system Incidence Incisor Independent Scientist Award Industry 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 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 analytical method base career career development craniofacial density drinking water environmental chemistry epidemiology study experience in vivo malformation malignant mouth neoplasm men&apos s group microCT mid-career faculty mouse model novel oral biology perfluorooctanoic acid pollutant prenatal reproductive development 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开发新的环境预防和治疗策略因素相关的口腔疾病。该职业发展 K02 奖将提供受保护的时间 1) 获得骨骼组织物理分析方面的专业知识，包括 Micro-CT、FIB-SEM 和 QLF，2) 与环境健康科学专家建立合作关系场地。拟议的研究项目旨在表征氟化物对健康的影响牙齿上的污染物 PFAS（全氟烷基物质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 存在于饮料中 PFAS 可以在水和生物体（包括鱼类、动物和人类）中积聚，随着时间的推移坚持下去。实验动物研究表明PFAS可引起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 FTOH（PFOA 的前体）引起牙齿畸形，包括成釉细胞变性在啮齿动物门牙中。然而，检查 FTOH 如何改变牙齿表型（物理和组织学）是有限的，并且 FTOH 如何影响牙齿发育的分子机制很大程度上是未知的。我们的长期目标是确定 PFAS 不良反应的分子机制对牙发育的影响。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 如何影响体内的釉质生成。我们的中央假设 FTOH 会诱导 DNA 损伤和线粒体损伤，从而扰乱成釉细胞牙齿发育过程中的功能，导致牙釉质畸形。我们的假设是我们的初步数据表明 PFOA 抑制细胞增殖，诱导成釉细胞样细胞（LS8 细胞）的凋亡、DNA 损伤和线粒体损伤。影响拟议研究的目的是确定 PFAS 对牙齿发育的影响并强调牙齿畸形的分子机制。一旦 PFAS 产生不良影响在牙齿形成过程中发现，PFAS 可以被认为是牙齿形成的一个可能的致病因素。牙本质发生中的隐源性异常，包括磨牙切牙矿化低下（MIH）其病因尚不清楚。我们计划检验我们的中心假设并完成我们的总体目标通过追求特定目标来实现目标：确定 FTOH 对小鼠牙釉质表型的影响模型。