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

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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