Exploring the role of HOCI in skin photodamage, immunosuppression, and carcinogenesis

探索 HOCI 在皮肤光损伤、免疫抑制和癌变中的作用

基本信息

批准号：
9904653
负责人：
Georg T Wondrak
金额：
$ 18.51万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9904653
关键词：
Acute Allergic Contact Dermatitis Asthma Carcinogens Cell Culture Techniques Cell Death Cells Chemosensitization Chronic Cutaneous DNA Data Dendritic Cells Dependence Diagnosis Disease Disinfectants Disinfection Economic Burden Environmental Carcinogens Environmental Exposure Exposure to Genetic Genotoxic Stress Goals Health Human Hypersensitivity Hypochlorous Acid Immunosuppression Impairment Incidence Individual Inflammatory Injury Investigation Laboratories Langerhans cell Malignant Neoplasms Mediating Mediator of activation protein Modification Molecular Nature Outcome Oxidation-Reduction Oxidative Stress Oxides Photons Population Public Health Reporting Research Respiratory physiology Risk Role Severities Skin Skin Carcinoma Skin Tissue Solar Energy Stress Sun Exposure Sunburn Swimming Pools Testing Time Tissue Model Tissues Toxic Environmental Substances Translational Research UV Radiation Exposure UV carcinogenesis UV induced Ultraviolet Rays United States base carcinogenesis chlorination cost cytotoxic design environmental carcinogenesis experimental study exposed human population genome integrity genotoxicity global health immunotoxicity improved keratinocyte mouse model photoprotection prototype response skin barrier skin irritation skin photodamage sunlight-induced ultraviolet

项目摘要

PROJECT SUMMARY Hypochlorous acid (HOCl) is the active oxidizing principle released by standard swimming pool disinfectants used on a global scale, but the health consequences of human exposure inflicted by HOCl remain largely unknown, posing a major public health concern relevant to populations around the world. Environmental exposure to solar ultraviolet (UV) radiation is a causative factor in skin photocarcinogenesis, and immune suppression is a key mechanism underlying detrimental effects of acute and chronic UV exposure. Based on our prototype experiments, the proposed research will explore the molecular potentiation of UV-induced cutaneous and systemic damage by co-exposure to HOCl-based swimming pool disinfectants, examined in cell culture, skin tissue models, and mouse models of UV-induced skin damage and cancer. First, we will define the specific molecular mechanisms underlying HOCl-potentiation of solar UV-induced oxidative insult and genotoxic stress, examined in cultured skin cells and human epidermal tissue reconstructs (aim #1). Next, we will explore the potentiating role of HOCl co-exposure in established murine models of UV-induced acute photodamage (sunburn), systemic photoimmunosuppression, and photocarcinogenesis (aim #2). The

项目概要次氯酸 (HOCl) 是标准游泳池消毒剂释放的活性氧化成分在全球范围内使用，但人类接触次氯酸造成的健康后果在很大程度上仍然存在未知，构成与世界各地人口相关的重大公共卫生问题。环境的暴露于太阳紫外线 (UV) 辐射是皮肤光致癌的致病因素，而免疫抑制是急性和慢性紫外线暴露产生有害影响的关键机制。基于我们的原型实验，拟议的研究将探索紫外线诱导皮肤的分子增强通过细胞培养、皮肤检查，共同暴露于基于次氯酸的游泳池消毒剂造成的和系统性损害紫外线引起的皮肤损伤和癌症的组织模型和小鼠模型。首先我们来定义一下具体的 HOCl增强太阳紫外线诱导的氧化损伤和基因毒性应激的分子机制，在培养的皮肤细胞和人类表皮组织重建中进行检查（目标#1）。接下来我们将探讨 HOCl 共同暴露在已建立的紫外线诱导急性光损伤小鼠模型中的增强作用（晒伤）、系统性光免疫抑制和光致癌（目标#2）。这