• Katharina Müller-Dott, Horst Thiermann, Dirk Steinritz, and Tanja Popp.
• Bundeswehr Institute of Pharmacology and Toxicology, 80937, Munich, Germany; Walther-Straub-Institute of Pharmacology and Toxicology, LMU Munich, 80336, Munich, Germany. Electronic address: katharina1muellerdott@bundeswehr.org.
• Toxicol. Lett. 2020 Feb 1; 319: 197-203.

AbstractThe chemical warfare agent sulfur mustard (SM) affects all cells in the epidermis including melanocytes which are responsible for melanin synthesis. After exposure to SM, pigment abnormalities like hypo- and hyperpigmentation can occur. The underlying molecular pathomechanisms of SM exposure on human melanogenesis have not been elucidated so far. In our study, we investigated the effect of SM on human melanocytes and melanogenesis. Normal human epidermal melanocytes (NHEM) were used as in vitro model and they were exposed to different concentrations of SM (4.5 μM-100 μM). Melanin production was analyzed by absorption measurements at 405 nm. In addition, quantitative real-time PCR (qPCR) and Western blot experiments were performed to determine the expression of essential melanogenesis-related proteins including tyrosinase (TYR), tyrosinase-related protein (TRP) 1 and 2 and microphthalmia transcription factor (MITF). Our findings demonstrated that exposure to low SM concentrations increased melanin synthesis accompanied with an increase in protein expression. In contrast, high SM concentrations led to decreased melanin content and a downregulation in expression of all investigated melanogenesis-associated proteins. We concluded that low SM concentrations may cause hyperpigmentation while high SM concentrations decreased melanin content which may explain hypopigmented skin areas in SM exposed patients.Copyright © 2019 Elsevier B.V. All rights reserved.

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