title: Mechanistic toxicity assessment of nanomaterials by whole-cell-array stress genes expression analysis.
abstract: This study performed mechanistic toxicity assessment of nanosilver (nAg) and nanotitanium dioxide anatase (nTiO2_a) via toxicogenomic approach, employing a whole-cell-array library consisting of 91 recombinated Escherichia coli K12 strains with transcriptional GFP-fusions covering most known stress response genes. The results, for the first time, revealed more detailed transcriptional information on the toxic mechanism of nAg and nTiO2_a, and led to a better understanding of the mode of action (MOA) of metal and metal oxide nanomaterials (NMs). The detailed pathways network established for the oxidative stress system and for the SOS (DNA damage) repair system based on the temporal gene expression profiling data revealed the relationships and sequences of key genes involved in these toxin response systems. Both NMs were found to cause oxidative stress as well as cell membrane and transportation damage. Genotoxicity and DNA damage were also observed, although nTiO2_a induced SOS response via previously identified pathway and nAg seemed to induce DNA repair via a pathway different from SOS. We observed that the NMs at lower concentration tend to induce more chemical-specific toxicity response, while at higher concentrations, more general global stress response dominates. The information-rich real-time gene expression data allowed for identification of potential biomarkers that can be employed for specific toxin detection and biosensor developments. The concentration-dependent gene expression response led to the determination of the No Observed Transcriptional Effect Level (NOTEL) values, which can be potentially applied in the regulatory and risk assessment framework as an alternative toxicity assessment end point.
authors.affiliation: Department of Civil & Environmental Engineering, 360 Huntington Avenue, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Gou
authors.forename: Annalisa
authors.initials: A
authors.lastname: Onnis-Hayden
authors.forename: April Z
authors.initials: AZ
authors.lastname: Gu
mesh_terms: D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005798:Genes, Bacterial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D012834:Silver / Q000633:toxicity*; D046888:Tissue Array Analysis; D014025:Titanium / Q000633:toxicity*
chemical_list: D009153:Mutagens; C009495:titanium dioxide; D012834:Silver; D014025:Titanium