Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea.
Department of Health, Environment and Safety, Eulji University, Seongnam 34824, Republic of Korea.
Ecotoxicol Environ Saf. 2019 Sep 30;180:326-332. doi: 10.1016/j.ecoenv.2019.05.003. Epub 2019 May 14.
Aniline and aniline derivatives have been widely used in the production of pesticides, pharmaceuticals, cosmetic, dyes, rubber, and adhesives products. These chemicals can easily be released into the environment through industrial and municipal discharges or as degradation byproducts. Several studies have suggested that aniline and some of its derivatives could cause reproductive toxicity in aquatic organisms. However, knowledge on the endocrine disruption potentials of these chemicals is limited only to aniline and associated mechanisms are rarely investigated. The objective of this study was to investigate the potential of major aniline derivatives, i.e., 3,4-dichloroaniline (3,4-DCA), 1-naphthylamine (1-NPA), and 4,4'-methylenedianiline (4,4'-MDA), to disrupt sex steroid production and other biological processes. For this purpose, the human adrenal H295R cell line and adult male zebrafish (Danio rerio) were used. In the H295R cell line, all tested aniline derivatives decreased testosterone (T) levels. Regulatory changes of several steroidogenic genes, i.e., down-regulation of StAR or CYP17 genes, and up-regulation of CYP19A, observed in the H295R cells could explain the sex hormone disruption. In male zebrafish, generally similar directions of changes, i.e., decreases in T levels and increased E2/T ratios, were observed. Again, down-regulation of key steroidogenic genes such as cyp17 or 3β-hsd, but slight up-regulation of cyp19a gene observed in the fish could explain the sex hormone changes. The results of our study demonstrate that all tested aniline derivatives could influence steroidogenesis and disrupt sex hormone balance toward reduced androgenicity. Consequences of anti-androgenicity following long-term exposure warrant further investigation.
苯胺和苯胺衍生物广泛应用于农药、制药、化妆品、染料、橡胶和粘合剂产品的生产。这些化学物质可以通过工业和城市排放或作为降解副产物轻易释放到环境中。有几项研究表明，苯胺及其某些衍生物可能对水生生物造成生殖毒性。然而，这些化学物质的内分泌干扰潜力的知识仅限于苯胺，相关机制很少被研究。本研究的目的是研究主要苯胺衍生物，即 3,4-二氯苯胺（3,4-DCA）、1-萘胺（1-NPA）和 4,4'-亚甲基二苯胺（4,4'-MDA），对性激素产生和其他生物过程的潜在干扰。为此，使用了人肾上腺 H295R 细胞系和成年雄性斑马鱼（Danio rerio）。在 H295R 细胞系中，所有测试的苯胺衍生物均降低了睾酮（T）水平。在 H295R 细胞中观察到的几个类固醇生成基因的调节变化，即 StAR 或 CYP17 基因的下调，以及 CYP19A 的上调，可以解释性激素的破坏。在雄性斑马鱼中，通常观察到类似的变化方向，即 T 水平降低和 E2/T 比值升高。同样，在鱼类中观察到关键类固醇生成基因如 cyp17 或 3β-hsd 的下调，但 cyp19a 基因的轻微上调可以解释性激素的变化。本研究的结果表明，所有测试的苯胺衍生物都可能影响类固醇生成，并破坏性激素平衡，导致雄激素降低。长期暴露后的抗雄激素作用的后果值得进一步研究。
