Abstract
The aim of this work was to use the yeast Saccharomyces cerevisiae as a tool for toxicogenomic studies of Engineered Nanomaterials (ENMs) risk assessment, in particular focusing on cadmium based quantum dots (CdS QDs). This model has been exploited for its peculiar features: a short replication time, growth on both fermentable and oxidizable carbon sources, and for the contextual availability of genome wide information in the form of genetic maps, DNA microarray, and collections of barcoded mutants. The comparison of the whole genome analysis with the microarray experiments (99.9% coverage) and with the phenotypic analysis of 4688 barcoded haploid mutants (80.2% coverage), shed light on the genes involved in the response to CdS QDs, both in vivo and in vitro. The results have clarified the mechanisms involved in the exposure to CdS QDs, and whether these ENMs and Cd2+ exploited different pathways of response, in particular related to oxidative stress and to the maintenance of mitochondrial integrity and function. Saccharomyces cerevisiae remains a versatile and robust alternative for organismal toxicological studies, with a high level of heuristic insights into the toxicology of more complex eukaryotes, including mammals.
Highlights
Engineered nanomaterials (ENMs) have a nanoscale level range of 1–100 nm, whose surface area can cause a higher reactivity
Pasquali et al (2017) [20] suggested a connection between cadmium sulphide quantum dots (CdS QDs)’ toxicity, mitochondria organization and functions. The preservation of this response has been retrieved in human cells (HepG2) in which the stress caused by CdS QDs increases the production of reactive oxygen species (ROS), and is able to trigger the mitochondria-mediated intrinsic apoptotic pathway, which involves genes related to apoptosis, oxidative stress response and autophagy [21]
312 genes up-regulated and 310 genes down-regulated in tThheropuregshenthcee mofic0ro.2a5rramyge·Lxp−1erniymsetanttisn, 3p1l2usge1n0e0s umpg-r·Leg−1uCladteSdQanDds 3w10ergeenidesendtoifwiend-reagt utlhaetefdixiend ththerpersehsoelndcse ooff 0+.12;5−1m(gT·aLb−l1esnySs1taatnindpSl2u)s, 1a0s0rmepgo·Lrt−e1dCindSthQeDosvwerelraepipdeedntsificaetdteartptlhoet firexperdetshernetsinhgoldthse odf i+s1tr;−ib1ut(iToanbloefstSh1e adnadtaSo2f),taresartempoernttesdvisn. cthoentorvoel rulanptrpeeadtesdca(tFtiegruprloetSr1e)p. rTehseengteinngesthwehdoissetriebxuptrieosnsioofn theexcdeaetdasotfhterefaixtmedenthtsrevssh. ocoldnstroofl +u2n;t−r2eawteedre(FsihgouwrenSi1n).tThheeugpe-naensdwdhoowsene-rxepgrueslasitoedn ehxecaetemdaspths e(Ffiixgeudre th1r)e. sholds of +2;−2 were shown in the up- and down-regulated heatmaps (Figure 1)
Summary
Engineered nanomaterials (ENMs) have a nanoscale level range of 1–100 nm, whose surface area can cause a higher reactivity. The high level of functional conservation between yeast genes and their orthologs in higher eukaryotes, including human orthologs, makes yeast a useful system to assess the toxicological mechanisms underlying the response to a wide range of ENMs [16,17,18,19]. In recent years, this model organism allowed elucidating the phenomic implications related to CdS QDs exposure, revealing the complex networks of interaction in which the genes HSC82, ALD3 and DSK2 played key roles [16]. A comparison with the results obtained in higher eukaryotes including human cells was consistent with yeast as a toxicological model [21]
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