Health Effects of the Fluorinated Pollutants; PFAS on Enamel Development

氟化污染物对健康的影响；

• 批准号: 10827647
• 负责人: Maiko Suzuki
• 金额: $ 5.82万
• 依托单位: NOVA SOUTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 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/10827647
• 关键词: Health; Effects; Fluorinated; Pollutants; PFAS

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 病理生理学并为环境因素相关的疾病制定新的预防和治疗策略 口腔疾病。该职业发展 K02 奖项将提供受保护的时间 1) 来获得以下方面的专业知识 骨骼组织的物理分析，包括 Micro-CT、FIB-SEM 和 QLF，以及 2) 建立协作 与环境健康科学领域专家的关系。拟议的研究项目旨在 描述氟化污染物 PFAS（全氟烷基物质和多氟烷基物质或 有机氟化合物）对牙齿发育的影响。 PFAS 是一组人造有机氟化合物 化合物，包括全氟辛酸 (PFOA) 和 PFOA 前体、氟调聚物醇 (FTOH)。 PFAS 不易在环境中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）中积聚并持续存在 时间。实验动物研究表明，PFAS 可导致肿瘤并对生殖能力产生不利影响， 发育和免疫系统。先前的研究表明，FTOH（PFOA 的前体）会诱导 牙齿畸形，包括啮齿动物门牙的成釉细胞变性。然而，检查如何 FTOH 改变牙齿表型（物理和组织学）的能力有限，其分子机制 FTOH 对牙齿发育的影响目前尚不清楚。我们的长期目标是确定分子 PFAS 对牙发育不良影响的机制。我们的总体目标是建立 PFAS （危险化学品）在动物模型中的使用并确定 FTOH 如何影响体内的釉质生成。我们的 中心假设是 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。我们的假设已经制定 根据我们的初步数据显示，PFOA 抑制细胞增殖、诱导细胞凋亡、DNA 损伤 以及成釉细胞样细胞（LS8 细胞）中的线粒体损伤。拟议研究的影响是定义 PFAS 对牙齿发育的影响并强调牙齿发育的分子机制 畸形。一旦发现 PFAS 对牙齿形成有不利影响，PFAS 就可以被视为一种 牙本质发生中隐源性异常的可能致病因素，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 通过追求特定目标来实现我们的总体目标：确定 FTOH 对牙釉质表型的影响 鼠标模型。