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
Hypochlorous acid (HOCl) is the active oxidizing principle released by standard disinfectants used on a global scale, but the health consequences of chlorination stress inflicted by HOCl-exposure, remains largely unknown, posing a major public health concern relevant to populations around the world. Exposure to specific environmental toxicants is an established cause underlying impairment of skin barrier function and adverse health effects, and cumulative evidence indicates that synergistic interactions between different environmental carcinogens greatly potentiate environmental carcinogenesis. Based on our prototype experiments, the proposed research will explore the adverse health effects caused by the combined exposure to solar ultraviolet (UV) radiation and chlorination stress (HOCl-coexposure), examined in cell culture, reconstructed human skin, and mouse models of sunlight-induced damage (sunburn, systemic immune suppression, and cancer). The global importance of human exposure to chlorination stress mediated by HOCl creates an urgent need for detailed molecular investigations met by the exploratory and translational research pursued in this R21 project.