School of Health Sciences, Purdue University, West Lafayette, IN, USA.
Metabolite Profiling Facility, Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA.
Neurotoxicol Teratol. 2021 May-Jun;85:106971. doi: 10.1016/j.ntt.2021.106971. Epub 2021 Mar 10.
Atrazine (ATZ) is the second most commonly applied agricultural herbicide in the United States. Due to contamination concerns, the U.S. EPA has set the maximum contaminant level in potable water sources at 3 parts per billion (ppb; μg/l). Depending on the time of year and sampling location, water sources often exceed this limit. ATZ is an endocrine disrupting chemical in multiple species observed to target the neuroendocrine system. In this study the zebrafish vertebrate model was used to test the hypothesis that a developmental ATZ exposure generates metabolites similar to those found in mammals and alters morphology and behavior in developing larvae. Adult AB zebrafish were bred, embryos were collected, and exposed to 0, 0.3, 3, or 30 ppb ATZ from 1 to 120 h post fertilization (hpf). Targeted metabolomic analysis found that zebrafish produce the same major ATZ metabolites as mammals: desethyl atrazine (DEA), deisopropyl atrazine (DIA), and diaminochloroatrazine (DACT). The visual motor response test at 120 hpf detected hyperactivity in larvae in the 0.3 ppb treatment group and hypoactivity in the 30 ppb treatment group (p < 0.05). Further analysis into behavior during the dark and light phases showed zebrafish larvae exposed to 0.3 ppb ATZ had an increase in total distance moved in the first light phase and time spent moving in the first dark and light phases (p < 0.05). Alternatively, a decrease in total distance moved was observed in the second and third dark phases in zebrafish exposed to 30 ppb ATZ (p < 0.05). No significant differences were observed for any of the morphological measurements following ATZ exposure from 1 to 120 hpf (p > 0.05). These findings suggest that a ATZ exposure during early development generates metabolite profiles similar to mammals and leads to behavioral alterations supporting ATZ as a neurodevelopmental toxicant.
阿特拉津（ATZ）是美国应用第二广泛的农业除草剂。由于受到污染的担忧，美国环保署已将饮用水源中最大污染物水平设定为 3 十亿分之几（ppb；μg/L）。根据一年中的时间和采样地点的不同，水源经常超过这一限制。ATZ 是一种在多种观察到针对神经内分泌系统的内分泌干扰化学物质。在这项研究中，使用斑马鱼脊椎动物模型来检验以下假设，即发育中的 ATZ 暴露会产生与哺乳动物中发现的相似的代谢物，并改变发育中幼虫的形态和行为。成年 AB 斑马鱼繁殖，收集胚胎，并从受精后 1 至 120 小时（hpf）暴露于 0、0.3、3 或 30 ppb ATZ。靶向代谢组学分析发现，斑马鱼产生与哺乳动物相同的主要 ATZ 代谢物：去乙基阿特拉津（DEA）、去异丙基阿特拉津（DIA）和二氨基氯代阿特拉津（DACT）。在 120 hpf 进行的视觉运动反应测试中，在 0.3 ppb 处理组中检测到幼虫的过度活跃，在 30 ppb 处理组中检测到活动减少（p<0.05）。对黑暗和光照阶段的行为进行进一步分析表明，暴露于 0.3 ppb ATZ 的斑马鱼幼虫在第一光照阶段的总移动距离增加，并且在第一黑暗和光照阶段的移动时间增加（p<0.05）。相反，在暴露于 30 ppb ATZ 的第二和第三黑暗阶段观察到总移动距离减少（p<0.05）。在从 1 至 120 hpf 暴露于 ATZ 后，未观察到任何形态测量的显著差异（p>0.05）。这些发现表明，早期发育过程中的 ATZ 暴露会产生与哺乳动物相似的代谢物谱，并导致行为改变，支持 ATZ 作为一种神经发育毒性物质。
