The Role of Environmental Chlorination Stress and Solar Ultraviolet Radiation in Skin Inflammation and Carcinogenesis

Abstract

A multitude of extrinsic environmental factors (referred to in their entirety as the ‘skin exposome’)impact structure and function of skin and its corresponding cellular components. The complex (i.e. additive, antagonistic, or synergistic) interactions between multiple extrinsic (exposome) and intrinsic (biological) factors are important determinants of skin health outcomes. Here, we have investigated the role of hypochlorous acid (HOCl) as an emerging component of the skin exposome serving molecular functions as an innate immune factor, environmental toxicant, and topical chemopreventive agent targeting solar UV-induced skin cancer. Our studies have explored the interaction between solar UV and HOCl-related environmental co-exposures identifying a heretofore unrecognized photo-chemopreventive activity of topical HOCl and chlorination stress that blocks inflammation and tumorigenic progression in UV-induced high-risk SKH-1 mouse skin, a finding in contrast with the pro-inflammatory and UV-enhancing effects of topical trichloroisocyanuric acid (TCIC), a common chloramine-type freshwater disinfectant. These observations on epithelial health and chlorination stress, explored for the first time in the context of skin exposure to chlorinated fresh water used for swimming pool disinfection, indicate a heretofore unrecognized role of chlorination stress as an environmental determinant of human epithelial health. We also demonstrate that reconstructed human gingiva (EpiGingivalTM), a gastrointestinal tissue with remarkable histological similarity to stratified skin, is subject to topical HOCl/TCIC-induced chlorination stress as a result of exposure to environmentally relevant dose regimens. Given the daily exposure of billions of people to chlorinated fresh water, our findings deserve future examinations that define cutaneous and gastrointestinal epithelial effects of freshwater chlorination relevant to human populations on a global scale.