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有关的环境因素病理生理学并为环境发展新颖的预防和治疗策略与因子相关的口腔疾病。这个职业发展K02奖将为受保护时间1）在骨骼组织的物理分析方面获得专业知识，包括Micro-CT，FIB-SEM和 QLF和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的健康影响牙齿上的污染物PFAS（每种和多氟烷基物质或有机荧光化合物）发展。 PFA是一组人造的有机氟化化合物，包括全氟辛酸（PFOA）和PFOA前体，氟醇醇（FTOHS）。 PFA会这样做不容易在环境中崩溃，并且是水溶性的。 PFA可以在喝酒中找到水和生物有机体，包括鱼，动物和人类，PFA可以建立和随着时间的流逝。实验室动物研究表明，PFA会引起肿瘤和不良对生殖，发育和免疫系统的影响。先前的研究表明 FTOHS（PFOA的前体）诱导的牙齿畸形，包括成木板的变性在啮齿动物门牙中。但是，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未知。我们的长期目标是确定PFA逆境的分子机制对牙胎发生的影响。我们的总体目标是建立PFA（危险化学物质）在动物模型中使用，并确定FTOH如何影响体内的没有变性。我们的中心假设是FTOHS诱导DNA损伤和线粒体损伤对烧焦的amelebolbolmbolbast 牙齿发育过程中的功能导致牙釉质畸形。我们的假设一直是根据我们的初步数据制定，表明PFOA抑制细胞增殖，诱导成成布细胞（LS8细胞）中的细胞凋亡，DNA损伤和线粒体损伤。影响拟议的研究是定义PFA对牙齿发育的影响并突出显示涉及牙齿畸形的分子机制。一旦PFA不良影响在形成牙齿中，PFA被视为可能的休闲因素牙本质发生中的隐态异常，包括摩尔门牙降压（MIH）病因是未知的。我们计划测试我们的中心假设并完成整体通过追求特定目的的目标：确定对鼠标搪瓷表型的影响模型。