化学品是影响人类健康的代表性环境因素。最近,外部暴露于一种化学物质的罗得诺(RD)引起的化学白斑病,获得性斑片状色素沉着减退,大约2万亚洲人。为了预防此类悲剧,需要开发一种危险评估系统,以准确确定可诱导白细胞的化学物质。人类案例研究显示了6种化学物质,包括RD,具有组成型白皮病诱导型效力和3种具有光敏性但不是组成型白皮病诱导型效力的化学物质。在这项研究中,我们先前开发的使用小鼠尾部皮肤的体内风险评估系统研究了6种阳性和3种阴性对照化学品,无论是否存在组成型白皮病诱导效力.根据验证结果,本研究旨在开发一种体外危害评估系统,以正确确定具有组成型白皮病诱导效力的化学物质。不出所料,外部暴露于6种阳性对照化学品,但不是外部暴露于3种阴性对照化学品,导致小鼠尾巴皮肤中组成型白斑病的发展,皮肤黑色素水平降低,黑素细胞数量减少。此外,通过是否存在内质网(ER)应激诱导,正确区分了6种阳性对照和3种阴性对照化学物质,但不是通过酪氨酸酶依赖性细胞死亡或活性氧(ROS)的产生,在永生化的正常黑素细胞中。使用尾皮的危害评估系统可以是可靠的体内工具,可以可靠地确定用于组成型白皮病诱导的化学物质的化学效力。专注于正常黑素细胞中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,用于准确评估具有白斑病诱导性的化学物质。因此,这项研究通过开发预防环境因素相关疾病的筛查系统为环境学做出了贡献.
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.