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酿酒酵母突变体的全基因组纳米毒理学筛选揭示了硫化镉量子点耐受性和敏感性的基础。

A genome-wide nanotoxicology screen of Saccharomyces cerevisiae mutants reveals the basis for cadmium sulphide quantum dot tolerance and sensitivity.

作者信息

Marmiroli M, Pagano L, Pasquali F, Zappettini A, Tosato V, Bruschi C V, Marmiroli N

机构信息

a Department of Life Sciences , University of Parma , Parma , Italy .

b IMEM-CNR , Parma , Italy , and.

出版信息

Nanotoxicology. 2016;10(1):84-93. doi: 10.3109/17435390.2015.1019586. Epub 2015 May 4.

DOI:10.3109/17435390.2015.1019586
PMID:25938282
Abstract

The use of cadmium sulphide quantum dots (CdS QDs) is increasing, particularly in the electronics industry. Their size (1-10 nm in diameter) is, however, such that they can be taken up by living cells. Here, a bakers' yeast (Saccharomyces cerevisiae) deletion mutant collection has been exploited to provide a high-throughput means of revealing the genetic basis for tolerance/susceptibility to CdS QD exposure. The deletion of 112 genes, some associated with the abiotic stress response, some with various metabolic processes, some with mitochondrial organization, some with transport and some with DNA repair, reduced the level of tolerance to CdS QDs. A gene ontology analysis highlighted the role of oxidative stress in determining the cellular response. The transformation of sensitive mutants with centromeric plasmids harbouring DNA from a wild type strain restored the wild type growth phenotype when the complemented genes encoded either HSC82, DSK2 or ALD3. The use of these simple eukaryote knock-out mutants for functional toxicogenomic analysis will inform studies focusing on higher organisms.

摘要

硫化镉量子点(CdS QDs)的应用正在增加,尤其是在电子工业中。然而,它们的尺寸(直径为1 - 10纳米)使得它们能够被活细胞摄取。在此,利用面包酵母(酿酒酵母)缺失突变体文库提供了一种高通量方法,以揭示对CdS QD暴露耐受性/敏感性的遗传基础。112个基因的缺失降低了对CdS QDs的耐受水平,这些基因有些与非生物胁迫反应相关,有些与各种代谢过程相关,有些与线粒体组织相关,有些与转运相关,还有些与DNA修复相关。基因本体分析突出了氧化应激在决定细胞反应中的作用。当互补基因编码HSC82、DSK2或ALD3时,用携带野生型菌株DNA的着丝粒质粒转化敏感突变体可恢复野生型生长表型。使用这些简单的真核生物敲除突变体进行功能毒理基因组学分析将为针对高等生物的研究提供信息。

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