Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education)/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University , Tianjin 300071, China.
Environ Sci Technol. 2017 Jul 18;51(14):7861-7871. doi: 10.1021/acs.est.7b01922. Epub 2017 Jun 28.
Developmental toxicity is a critical issue in nanotoxicity. However, very little is known about the effects of graphene oxide (GO, a widely used carbon material) at predicted environmental concentrations on biological development or the specific molecular mechanisms. The present study established that the development of zebrafish embryos exposed to trace concentrations (1-100 μg/L) of GO was impaired because of DNA modification, protein carbonylation and excessive generation of reactive oxygen species (ROS), especially the superoxide radical. Noticeably, there was a nonmonotonic response of zebrafish developmental toxicity to GO at μg/L to mg/L levels. Transcriptomics analysis revealed that disturbing collagen- and matrix metalloproteinase (MMP)-related genes affected the skeletal and cardiac development of zebrafish. Moreover, metabolomics analysis showed that the inhibition of amino acid metabolism and the ratios of unsaturated fatty acids (UFAs) to saturated fatty acids (SFAs) contributed to the above developmental toxicity. The present work verifies the developmental toxicity of GO at trace concentrations and illustrates for the first time the specific molecular mechanisms thereof. Because of the potential developmental toxicity of GO at trace concentrations, government administrators and nanomaterial producers should consider its potential risks prior to the widespread environmental exposure to GO.
发育毒性是纳米毒性的一个关键问题。然而，对于预测环境浓度下的氧化石墨烯（GO，一种广泛使用的碳材料）对生物发育的影响，以及特定的分子机制，人们知之甚少。本研究表明，由于 DNA 修饰、蛋白质羰基化和活性氧（ROS）的过度产生，尤其是超氧自由基，暴露于痕量浓度（1-100μg/L）GO 的斑马鱼胚胎的发育受到损害。值得注意的是，GO 在μg/L 到 mg/L 水平对斑马鱼发育毒性的非单调响应。转录组学分析显示，扰乱胶原蛋白和基质金属蛋白酶（MMP）相关基因会影响斑马鱼的骨骼和心脏发育。此外，代谢组学分析表明，氨基酸代谢的抑制以及不饱和脂肪酸（UFAs）与饱和脂肪酸（SFAs）的比例与上述发育毒性有关。本工作验证了 GO 在痕量浓度下的发育毒性，并首次阐明了其特定的分子机制。由于 GO 在痕量浓度下具有潜在的发育毒性，政府管理者和纳米材料生产者在 GO 广泛暴露于环境之前，应考虑其潜在风险。
