Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Activities of the Institute of Innovation for Future Society of Nagoya University, Japan; Voluntary Body for International Healthcare in Universities, Nagoya, Aichi, Japan.
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Voluntary Body for International Healthcare in Universities, Nagoya, Aichi, Japan.
Environ Pollut. 2024 Sep 1;356:124508. doi: 10.1016/j.envpol.2024.124508. Epub 2024 Aug 1.
Chemicals are representative environmental factors that affect human health. Recently, external exposure to a chemical of rhododenol (RD) caused chemical leukoderma, an acquired patchy hypopigmentation, in about 20,000 Asian people. The development of a hazard assessment system for accurate determination of leukoderma-inducible chemicals is required for the prevention of such tragedies. Case studies in humans have shown 6 chemicals, including RD, with a constitutive leukoderma-inducible potency and 3 chemicals with a photosensitive but not a constitutive leukoderma-inducible potency. In this study, the 6 positive and 3 negative control chemicals with or without constitutive leukoderma-inducible potencies were investigated by our previously developed in vivo hazard assessment system using tail skin of mice. Based on the results of validation, this study aimed to develop an in vitro hazard assessment system to correctly determine chemicals with a constitutive leukoderma-inducible potency. As expected, external exposure to the 6 positive control chemicals, but not external exposure to the 3 negative control chemicals, resulted in development of constitutive leukoderma in mouse tail skin with a decreased level of skin melanin and decreased number of melanocytes. Moreover, the 6 positive and 3 negative control chemicals were correctly distinguished by the presence or absence of endoplasmic reticulum (ER) stress induction, but not by tyrosinase-dependent cell death or production of reactive oxygen species (ROS), in immortalized normal melanocytes. The hazard assessment system using tail skin could be a solid in vivo tool to reliably determine the chemical potency of a chemical for constitutive leukoderma induction. The hazard assessment system focusing on ER stress induction in normal melanocytes might be a novel and convenient in vitro tool for accurately evaluating chemicals with leukoderma-inducible potencies. Thus, this study contributed to environmentology through the development of a screening system for preventing an environmental factor-related disease.
化学物质是影响人类健康的代表性环境因素之一。最近，约 2 万名亚洲人因接触到一种名为二氢杨梅素（RD）的化学物质而导致化学性白斑病，这是一种后天获得的斑驳性色素减退症。为了预防此类悲剧的发生，需要建立一个准确评估致白化病化学物质的危害评估系统。人体病例研究表明，包括 RD 在内的 6 种化学物质具有固有致白化病的能力，而 3 种化学物质具有光致敏性但不具有固有致白化病的能力。在这项研究中，我们使用小鼠尾部皮肤，通过之前开发的体内危害评估系统，研究了具有固有致白化病能力的 6 种阳性对照化学物质和 3 种阴性对照化学物质。基于验证结果，本研究旨在开发一种体外危害评估系统，以正确确定具有固有致白化病能力的化学物质。正如预期的那样，仅接触 6 种阳性对照化学物质而非 3 种阴性对照化学物质，会导致小鼠尾部皮肤出现固有白化病，皮肤黑色素水平降低，黑素细胞数量减少。此外，在永生化正常黑素细胞中，通过内质网（ER）应激诱导的存在或不存在，而不是通过酪氨酸酶依赖性细胞死亡或活性氧（ROS）的产生，可正确区分 6 种阳性对照和 3 种阴性对照化学物质。使用尾部皮肤的危害评估系统可能是一种可靠的体内工具，可用于确定化学物质固有致白化病的能力。关注正常黑素细胞中 ER 应激诱导的危害评估系统可能是一种新颖且方便的体外工具，可用于准确评估具有致白化病能力的化学物质。因此，通过开发一种预防环境因素相关疾病的筛选系统，本研究为环境学做出了贡献。
