Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Ontario, Canada.
Department of Biology, Centre for Advanced Research in Environmental Genomics and the Collaborative Program in Chemical and Environmental Toxicology, University of Ottawa, Ottawa, Ontario, Canada.
PLoS One. 2018 Mar 19;13(3):e0193111. doi: 10.1371/journal.pone.0193111. eCollection 2018.
Engineered nanomaterials (ENMs) are increasingly incorporated into a variety of commercial applications and consumer products; however, ENMs may possess cytotoxic properties due to their small size. This study assessed the effects of two commonly used ENMs, zinc oxide nanoparticles (ZnONPs) and silver nanoparticles (AgNPs), in the model eukaryote Saccharomyces cerevisiae. A collection of ≈4600 S. cerevisiae deletion mutant strains was used to deduce the genes, whose absence makes S. cerevisiae more prone to the cytotoxic effects of ZnONPs or AgNPs. We demonstrate that S. cerevisiae strains that lack genes involved in transmembrane and membrane transport, cellular ion homeostasis, and cell wall organization or biogenesis exhibited the highest sensitivity to ZnONPs. In contrast, strains that lack genes involved in transcription and RNA processing, cellular respiration, and endocytosis and vesicular transport exhibited the highest sensitivity to AgNPs. Secondary assays confirmed that ZnONPs affected cell wall function and integrity, whereas AgNPs exposure decreased transcription, reduced endocytosis, and led to a dysfunctional electron transport system. This study supports the use of S. cerevisiae Gene Deletion Array as an effective high-throughput technique to determine cellular targets of ENM toxicity.
工程纳米材料(ENMs)越来越多地被应用于各种商业用途和消费产品中;然而,由于其尺寸较小,ENMs 可能具有细胞毒性。本研究评估了两种常用的工程纳米材料,氧化锌纳米粒子(ZnONPs)和银纳米粒子(AgNPs),在真核生物酿酒酵母中的作用。使用了约 4600 株酿酒酵母缺失突变体菌株,以推断出使酿酒酵母更容易受到 ZnONPs 或 AgNPs 细胞毒性影响的基因。我们证明,缺乏参与跨膜和膜运输、细胞离子稳态以及细胞壁组织或生物发生的基因的酿酒酵母菌株对 ZnONPs 表现出最高的敏感性。相比之下,缺乏参与转录和 RNA 加工、细胞呼吸以及内吞作用和小泡运输的基因的菌株对 AgNPs 表现出最高的敏感性。辅助实验证实,ZnONPs 影响细胞壁功能和完整性,而 AgNPs 暴露会降低转录、减少内吞作用,并导致电子传递系统功能失调。本研究支持使用酿酒酵母基因缺失阵列作为一种有效的高通量技术来确定 ENM 毒性的细胞靶标。