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; 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有关的环境因素 病理生理学并为环境因素相关的新型预防和治疗策略 口腔疾病。这项职业发展K02奖将为受保护的时间1）获得专业知识 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 表征了氟化污染物PFA（每种和多氟烷基物质或 牙齿发育的有机氟化合物）。 PFA是一组人造的有机氟 化合物，包括全氟辛酸（PFOA）和PFOA前体，荧光素体醇（FTOHS）。 PFA在环境中不容易崩溃，并且是水溶性的。 PFA可以在喝酒中找到 水和活生物体，包括鱼，动物和人类，PFA可以在这里堆积并持续 时间。实验室动物研究表明，PFA会对肿瘤引起肿瘤和对生殖力的不利影响， 开发和免疫系统。先前的研究表明，FTOHS（PFOA的前体）诱导 牙齿畸形，包括啮齿动物切牙中的成成细胞的变性。但是，考察如何 FTOHS改变牙齿表型（物理和组织学）是有限的，并且分子机制的方式 FTOH会影响牙齿发育，这在很大程度上尚不清楚。我们的长期目标是确定分子 PFAS不利影响牙肠发生的机制。我们的总体目标是建立PFA （危险化学）在动物模型中使用，并确定FTOH在体内如何影响休闲发生。我们的 中心假设是FTOHS诱导DNA损伤和线粒体损伤对烧焦的amellast 牙齿发育过程中的功能导致牙釉质畸形。我们的假设已被提出 根据我们的初步数据，表明PFOA抑制细胞增殖，诱导凋亡，DNA损伤 和木质细胞样细胞（LS8细胞）中的线粒体损伤。拟议研究的影响是定义 PFA对牙齿发育的影响并突出牙齿涉及的分子机制 畸形。一旦在牙齿形成中鉴定出PFA的不良反应，PFA就可以被视为 牙齿发生的隐源性异常的可能因素，包括摩尔门牙 病因尚不清楚的低矿化（MIH）。我们计划检验我们的中心假设和 通过追求具体目标来实现我们的整体目标：确定对搪瓷表型的影响 鼠标模型。