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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

项目总结

项目成果

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Georg T Wondrak其他文献

GLO1 Downregulation in Human Renal Cell Carcinoma Enables Targeted Chemotherapeutic Intervention Using Methylglyoxal as Cytotoxic Heat Shock Inducer

DOI：
10.1016/j.freeradbiomed.2010.10.184
发表时间：
2010-01-01
期刊：
Conference abstract
影响因子：
作者：
Christopher M Cabello;Shuxi Qiao;Warner B Bair;Angela L Davis;Jessica L Lesson;Georg T Wondrak
通讯作者：
Georg T Wondrak

218 - Repurposing the Electron Transfer Reactant PMS (Phenazine Methosulfate) as an Experimental Redox Chemotherapeutic for the Superoxide-Dependent Apoptotic Elimination of Malignant Cells

DOI：
10.1016/j.freeradbiomed.2015.10.262
发表时间：
2015-10-01
期刊：
Conference abstract
影响因子：
作者：
Anh B Hua;Sophia L Park;Rebecca Justiniano;Mohammad Fazel;Christopher M Cabello;Georg T Wondrak
通讯作者：
Georg T Wondrak

144 - The Clinical Antimalarial Mefloquine Induces Lethal ER and Oxidative Stress Targeting BRAF-Kinase Inhibitor-Resistant Malignant Melanoma Cells

DOI：
10.1016/j.freeradbiomed.2015.10.185
发表时间：
2015-10-01
期刊：
Conference abstract
影响因子：
作者：
Sophia L Park;Tamara Steinfass;Georg T Wondrak
通讯作者：
Georg T Wondrak

326 - Acute Solar UV Exposure Generates Photodamage-Associated Protein Epitopes in Healthy Human Skin: Implications for Cutaneous Tumorigenesis

DOI：
10.1016/j.freeradbiomed.2014.10.223
发表时间：
2014-11-01
期刊：
Conference abstract
影响因子：
作者：
Joshua D Williams;Yira Bermudez;Fangru Lian;Koji Uchida;Sophia L Park;Georg T Wondrak
通讯作者：
Georg T Wondrak

251 - The Endogenous Tryptophan-Derived Photoproduct and AhR Agonist 6-Formylindolo[3,2-B]carbazole (FICZ) Is a Nanomolar Cutaneous Photosensitizer That Can Be Harnessed for the Oxidative Elimination of Skin Cancer Cells in Vitro and in Vivo

DOI：
10.1016/j.freeradbiomed.2015.10.298
发表时间：
2015-10-01
期刊：
Conference abstract
影响因子：
作者：
Rebecca Justiniano;Sophia L Park;Joshua D Williams;Daniel R Wieland;Georg T Wondrak
通讯作者：
Georg T Wondrak