Critical window of exposure of CMIT/MIT with respect to developmental effects on zebrafish embryos: Multi-level endpoint and proteomics analysis
Critical window of exposure of CMIT/MIT with respect to developmental effects on zebrafish embryos: Multi-level endpoint and proteomics analysis
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DOI：
10.1016/j.envpol.2020.115784
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发表时间：
2021-01-01
影响因子：
8.9
通讯作者：
Choi, Jinhee
中科院分区：
文献类型：
--
作者：
Chatterjee, Nivedita;Lee, Hyunho;Choi, Jinhee
导致韩国儿童肺部损伤的加湿器消毒化学品的全身毒性，特别是发育缺陷，仍有待阐明。本研究评估了造成韩国悲剧的主要杀菌剂之一 5-氯-2-甲基-4-异噻唑啉-3-酮/2甲基-4-异噻唑啉-3-酮 (CMIT/MIT) 的不利影响机制，并确定了生命早期暴露时最易受影响的发育阶段。为此，该研究旨在分析暴露斑马鱼 (Danio rerio) 胚胎在不同发育阶段的几个终点（形态、心率、行为、整体 DNA 甲基化、DNA 甲基转移酶 (dnmts) 的基因表达和蛋白质分析）。结果表明，CMIT/MIT 暴露会导致尾巴弯曲、心包水肿、心率改变、整体 DNA 高甲基化以及运动行为的显着改变。与形态学和生理学终点一致，生物信息学分析的蛋白质组学分析表明，抑制心肌收缩和能量代谢（氧化磷酸化）可能是 CMIT/MIT 介导的不良反应的关键潜在机制。简而言之，多级终点分析表明，对于 CMIT/MIT，最易受影响的暴露窗口为 < 6 hpf，其次是 < 48 hpf。这些结果可能会转化为对加湿器消毒剂的发育暴露影响的风险评估。 (C) 2020 Elsevier Ltd. 保留所有权利。
Systemic toxicity, particularly, developmental defects of humidifier disinfectant chemicals that have caused lung injuries in Korean children, remains to be elucidated. This study evaluated the mechanisms of the adverse effects of 5-chloro-2-methyl-4-isothiazoline-3-one/2methyl-4-isothiazolin-3-one (CMIT/MIT), one of the main biocides of the Korean tragedy, and identify the most susceptible developmental stage when exposed in early life. To this end, the study was designed to analyze several endpoints (morphology, heart rate, behavior, global DNA methylation, gene expressions of DNA methyl-transferases (dnmts) and protein profiling) in exposed zebrafish (Danio rerio) embryos at various developmental stages. The results showed that CMIT/MIT exposure causes bent tail, pericardial edema, altered heart rates, global DNA hypermethylation and significant alterations in the locomotion behavior. Consistent with the morphological and physiological endpoints, proteomics profiling with bioinformatics analysis suggested that the suppression of cardiac muscle contractions and energy metabolism (oxidative phosphorylation) were possible pivotal underlying mechanisms of the CMIT/MIT mediated adverse effects. Briefly, multi-level endpoint analysis indicated the most susceptible window of exposure to be < 6 hpf followed by < 48 hpf for CMIT/MIT. These results could potentially be translated to a risk assessment of the developmental exposure effects to the humidifier disinfectants. (C) 2020 Elsevier Ltd. All rights reserved.