Role of omics techniques in the toxicity testing of nanoparticles

Abstract

Nanotechnology is regarded as a key technology of the twenty-first century. Despite the many advantages of nanotechnology it is also known that engineered nanoparticles (NPs) may cause adverse health effects in humans. Reports on toxic effects of NPs relay mainly on conventional (phenotypic) testing but studies of changes in epigenome, transcriptome, proteome, and metabolome induced by NPs have also been performed. NPs most relevant for human exposure in consumer, health and food products are metal, metal oxide and carbon-based NPs. They were also studied quite frequently with omics technologies and an overview of the study results can serve to answer the question if screening for established targets of nanotoxicity (e.g. cell death, proliferation, oxidative stress, and inflammation) is sufficient or if omics techniques are needed to reveal new targets. Regulated pathways identified by omics techniques were confirmed by phenotypic assays performed in the same study and comparison of particle types and cells by the same group indicated a more cell/organ-specific than particle specific regulation pattern. Between different studies moderate overlap of the regulated pathways was observed and cell-specific regulation is less obvious. The lack of standardization in particle exposure, in omics technologies, difficulties to translate mechanistic data to phenotypes and comparison with human in vivo data currently limit the use of these technologies in the prediction of toxic effects by NPs.

Mass spectrometry-based proteomics for system-level characterization of biological responses to engineered nanomaterials

“…With the integration of quantitative proteomics along with other phenotypic assays in toxicological screening, we shall be able to learn many more details regarding regulatory mechanisms of cellular responses. The advantages of applying proteomics in toxicity screening of ENMs have also been recognized in several recent reviews [81,30]. Proteomics can not only identify cellular pathways that are typically targeted by traditional phenotypic assays, but also reveal novel pathways relevant to cellular responses to exposure.…”

“…Omics-based approaches such as transcriptomics have been applied extensively for profiling gene expression changes upon ENM exposure [25,27–30]. Although these studies provide valuable information on how ENMs alter gene expression, the changes at the mRNA level do not necessarily correlate with changes at the protein level.…”

Transcriptomics in Toxicogenomics, Part I: Experimental Design, Technologies, Publicly Available Data, and Regulatory Aspects

“…Thus, the false positive and/or negative results in conventional screening assays are due to interference caused by intracellular ENMs that affect the color, chemical activity, light scattering, etc. [80][81][82].…”

“…In general, Omics techniques have been supposed to exhibit lower interference due to the removal of the ENMs during the isolation of the analyte [81]. Unfortunately, even if the ENMs are removed by repeated wash-steps within the isolation procedure, the damage might have already been done when intracellular or cell membrane-bound ENMs interfere with the biological molecules that are used to assess toxicity [93].…”

Multi-omics analysis of ten carbon nanomaterials effects highlights cell type specific patterns of molecular regulation and adaptation

“…We and others already showed that ENMs are able to exert toxic effects on the respiratory system, by using animal exposure models (Kinaret et al, 2017a;Rydman et al, 2015;Rydman et al, 2014). Apart from the pathological responses, ENMs MOA has been investigated in different tissues (Kinaret et al, 2017b;Fröhlich, 2017;Costa and Fadeel, 2016), by analyzing the molecular perturbations that these materials are able to induce on the normal transcriptional program of exposed cells and tissues.…”