Health Effects of the Fluorinated Pollutants; PFAS on Enamel Development

氟化污染物对健康的影响；

• 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
• 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' s group; microCT; mid-career faculty; mouse model; novel; oral biology; perfluorooctanoic acid; pollutant; prenatal; reproductive development; skeletal tissue; skills; tumor

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 病理生理学和开发新的环境保护和治疗策略 与因素相关的口腔疾病。这项职业发展K02奖将提供保护 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，以及2)与环境健康科学专家建立合作关系 菲尔德。拟议的研究项目旨在描述氟化食品对健康的影响。 牙齿上的污染物全氟烷基化合物(全氟烷基和多氟烷基物质或有机氟化合物) 发展。全氟化铝是一组人造有机氟化合物，包括 全氟辛酸(全氟辛酸)和全氟辛酸前体--氟调聚体醇(FTOHs)。全氟辛烷磺酸 在环境中不易分解，且易溶于水。在饮酒中可以发现全氟辛烷磺酸 水和生物，包括鱼、动物和人类，全氟辛烷磺酸可以在这些地方建立和 随着时间的推移，坚持下去。实验动物研究表明，全氟辛烷磺酸可导致肿瘤和不良反应 对生殖、发育和免疫系统的影响。此前的研究表明， 全氟辛酸前体FTOHs诱导的牙齿畸形，包括成釉细胞变性 在啮齿动物的门牙上。然而，检查FTOHs如何改变牙齿表型(生理和 组织学)是有限的，FTOHs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。我们在这里的总体目标是建立PFAS(危险化学品) 在动物模型中使用，并确定FTOHs如何影响体内的成釉作用。我们的中央 假说FTOHs诱导扰动成釉细胞DNA损伤和线粒体损伤 在牙齿发育过程中起作用，导致牙釉质畸形。我们的假设是 根据我们的初步数据得出的配方显示，全氟辛酸抑制细胞增殖，诱导 成釉细胞样细胞(LS8细胞)的凋亡、DNA损伤和线粒体损伤。其影响 拟议的研究的目的是确定全氟化铝对牙齿发育的影响，并强调 牙齿畸形发生的分子机制。一旦全氟辛烷磺酸的不良影响 在牙齿形成中发现，PFAS可以被认为是一种可能的致病因素 牙本质形成中的隐源性异常，包括磨牙切牙下矿化 其病因尚不清楚。我们计划测试我们的中心假设，并实现我们的总体 目的探讨FTOH对小鼠牙釉质表型的影响 模特。