The 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.

中文翻译：

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硫芥对体外黑色素生成的影响

化学战剂硫芥 (SM) 会影响表皮中的所有细胞，包括负责黑色素合成的黑色素细胞。暴露于 SM 后，可能会发生色素异常，如色素沉着不足和色素沉着过度。迄今为止，SM 暴露对人类黑色素生成的潜在分子病理机制尚未阐明。在我们的研究中，我们研究了 SM 对人类黑色素细胞和黑色素生成的影响。正常人表皮黑色素细胞 (NHEM) 用作体外模型，并将它们暴露于不同浓度的 SM (4.5 μM-100 μM)。通过在 405 nm 处的吸收测量来分析黑色素的产生。此外，还进行了实时定量 PCR (qPCR) 和蛋白质印迹实验，以确定必需的黑色素生成相关蛋白的表达，包括酪氨酸酶 (TYR)、酪氨酸酶相关蛋白 (TRP) 1 和 2 以及小眼炎转录因子 (MITF)。我们的研究结果表明，暴露于低 SM 浓度会增加黑色素合成，同时增加蛋白质表达。相反，高 SM 浓度导致黑色素含量降低和所有研究的黑色素生成相关蛋白的表达下调。我们得出结论，低 SM 浓度可能导致色素沉着过度，而高 SM 浓度会降低黑色素含量，这可能解释了 SM 暴露患者的皮肤色素减退区域。高 SM 浓度导致黑色素含量降低和所有研究的黑色素生成相关蛋白的表达下调。我们得出结论，低 SM 浓度可能导致色素沉着过度，而高 SM 浓度会降低黑色素含量，这可能解释了 SM 暴露患者的皮肤色素减退区域。高 SM 浓度导致黑色素含量降低和所有研究的黑色素生成相关蛋白的表达下调。我们得出结论，低 SM 浓度可能导致色素沉着过度，而高 SM 浓度会降低黑色素含量，这可能解释了 SM 暴露患者的皮肤色素减退区域。