title: An in vitro assessment of panel of engineered nanomaterials using a human renal cell line: cytotoxicity, pro-inflammatory response, oxidative stress and genotoxicity.
abstract: BACKGROUND
  It has been shown that nanomaterials (NMs) are able to translocate to secondary tissues one of the important being the kidneys. Oxidative stress has been implicated as a possible mechanism for NM toxicity, hence effects on the human renal proximal tubule epithelial cells (HK-2) treated with a panel of engineered nanomaterials (NMs) consisting of two zinc oxide particles (ZnO - coated - NM 110 and uncoated - NM 111), two multi walled carbon nanotubes (MWCNT) (NM 400 and NM 402), one silver (NM 300) and five TiO2 NMs (NM 101, NRCWE 001, 002, 003 and 004) were evaluated.
  
  
  METHODS
  In order to assess the toxicological impact of the engineered NMs on HK-2 cells - WST-1 cytotoxicity assay, FACSArray, HE oxidation and the comet assays were utilised. For statistical analysis, the experimental values were compared to their corresponding controls using an ANOVA with Tukey's multiple comparison.
  
  
  RESULTS
  We found the two ZnO NMs (24 hr LC50 - 2.5 μg/cm2) and silver NM (24 hr LC50 - 10 μg/cm2) were highly cytotoxic to the cells. The LC50 was not attained in the presence of any of the other engineered nanomaterials (up to 80 μg/cm2). All nanomaterials significantly increased IL8 and IL6 production. Meanwhile no significant change in TNF-α or MCP-1 was detectable. The most notable increase in ROS was noted following treatment with the Ag and the two ZnO NMs. Finally, genotoxicity was measured at sub-lethal concentrations. We found a small but significant increase in DNA damage following exposure to seven of the ten NMs investigated (NM 111, NRCWE 001 and NRCWE 003 being the exception) with this increase being most visible following exposure to Ag and the positively charged TiO2.
  
  
  CONCLUSIONS
  While the NMs could be categorised as low and highly cytotoxic, sub-lethal effects such as cytokine production and genotoxicity were observed with some of the low toxicity materials.
authors.affiliation: Heriot-Watt University, School of Life Sciences, Edinburgh, EH14 4AS, UK. A.Kermanizadeh@hw.ac.uk
authors.forename: Ali
authors.initials: A
authors.lastname: Kermanizadeh
authors.forename: Sandra
authors.initials: S
authors.lastname: Vranic
authors.forename: Sonja
authors.initials: S
authors.lastname: Boland
authors.forename: Kevin
authors.initials: K
authors.lastname: Moreau
authors.forename: Armelle
authors.initials: A
authors.lastname: Baeza-Squiban
authors.forename: Birgit K
authors.initials: BK
authors.lastname: Gaiser
authors.forename: Livia A
authors.initials: LA
authors.lastname: Andrzejczuk
authors.forename: Vicki
authors.initials: V
authors.lastname: Stone
mesh_terms: D000818:Animals; D001698:Biomedical Engineering / Q000379:methods*; D002417:Cattle; D002460:Cell Line; D002461:Cell Line, Transformed; D003603:Cytotoxins / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D003603:Cytotoxins; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species