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.

铃木博士的最终研究目标是确定与颅面相关的环境因素 环境因素相关的病理生理和开发新的预防和治疗策略 口腔疾病。此K02职业发展奖将提供受保护的时间来获得以下方面的专业知识 对骨骼组织进行物理分析，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 描述含氟污染物全氟辛烷基磺酸(全氟烷基和多氟烷基物质或 有机氟化合物)对牙齿发育的影响。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，含氟调聚体醇(FTOHs)。 全氟辛烷磺酸在环境中不容易分解，而且是水溶性的。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，在这些生物中，全氟辛烷磺酸可以积聚并持续存在 时间到了。实验室动物研究表明，全氟辛烷磺酸会导致肿瘤和对生殖的不利影响， 发育和免疫系统。以往的研究表明，FTOHs(全氟辛酸的前体)可诱导 牙齿畸形，包括啮齿动物门牙中成釉细胞的退化。然而，审查是如何 FTOHs改变牙齿表型(物理和组织学)是有限的，其分子机制是如何 FTOH对牙齿发育的影响在很大程度上是未知的。我们的长期目标是识别分子 全氟辛烷磺酸对牙齿发育不利影响的机制。我们在这里的总体目标是建立PFAS (危险化学品)在动物模型中的使用，并确定FTOHs如何影响体内的成釉作用。我们的 中心假说是FTOHs诱导扰动的成釉细胞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。我们的假设已经公式化了 根据我们的初步数据显示，全氟辛酸抑制细胞增殖，诱导细胞凋亡，DNA损伤 成釉细胞样细胞(LS8细胞)线粒体损伤。拟议研究的影响是定义 全氟化铝对牙齿发育的影响及其分子机制的研究进展 畸形。一旦全氟辛烷磺酸在牙齿形成中的不利影响被确定，全氟辛烷磺酸可以被认为是一种 牙本质形成中隐源性异常的可能致病因素，包括磨牙切牙 病因不明的矿化过少(MIH)。我们计划测试我们的中心假设 通过追求特定的目标来实现我们的总体目标：确定FTOH对牙釉质表型的影响 老鼠模型。