PMID- 28705761
OWN - NLM
STAT- MEDLINE
DCOM- 20180509
LR  - 20180509
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 44
DP  - 2017 Oct
TI  - Factors of concern in a human 3D cellular airway model exposed to aerosols of 
      nanoparticles.
PG  - 339-348
LID - S0887-2333(17)30192-3 [pii]
LID - 10.1016/j.tiv.2017.07.006 [doi]
AB  - Mucilair 3D bronchial airway models, cultured at an air-liquid interface, were 
      exposed to aerosols of copper oxide (CuO) nanoparticles in Vitrocell air exposure 
      modules. Four cell donors, four exposure modules and four exposure concentrations 
      were varied within four different exposure sessions using a statistical 
      experimental design called a hyper-Graeco-Latin square. Analysis of variance 
      techniques were used to investigate the effects of these factors on release and 
      RNA expression of inflammation markers monocyte chemoattractant protein-1 (MCP-1) 
      interleukines 6 and 8 (IL-6 and IL-8) an cytotoxicity marker lactate 
      dehydrogenase (LDH) determined 24h after exposure. The same techniques were also 
      used to conduct a global analysis on RNA expressions of 10,000 genes. There were 
      no major signs of cytotoxicity. Release of IL-6 and MCP-1 was affected by CuO 
      concentration, and, for MCP-1, by donor variation. IL-8 release was not affected 
      by these factors. However, gene expression of all three inflammation markers was 
      strongly affected by CuO concentration but not by the other factors. Further, 
      among the 10,000 genes involved in the global analysis of RNA expression, 1736 
      were affected by CuO concentration, 704 by donor variation and 269 by variation 
      among exposure sessions. The statistical design permitted the assessment of the 
      effect of CuO nanoparticles on 3D airway models independently of technical or 
      experimental sources of variation. We recommend using such a design to address 
      all potential sources of variation. This is especially recommended if test 
      materials are expected to be less toxic than CuO, because the variation among the 
      concentration levels could then be close to the variation among donors or 
      exposure sessions.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Kooter, Ingeborg M
AU  - Kooter IM
AD  - The Netherlands Organization for Applied Scientific Research, TNO, P.O. Box 360, 
      3700 AJ Zeist, The Netherlands.
FAU - Grollers-Mulderij, Mariska
AU  - Grollers-Mulderij M
AD  - The Netherlands Organization for Applied Scientific Research, TNO, P.O. Box 360, 
      3700 AJ Zeist, The Netherlands.
FAU - Duistermaat, Evert
AU  - Duistermaat E
AD  - Triskelion BV, Zeist, The Netherlands.
FAU - Kuper, Frieke
AU  - Kuper F
AD  - The Netherlands Organization for Applied Scientific Research, TNO, P.O. Box 360, 
      3700 AJ Zeist, The Netherlands.
FAU - Schoen, Eric D
AU  - Schoen ED
AD  - The Netherlands Organization for Applied Scientific Research, TNO, P.O. Box 360, 
      3700 AJ Zeist, The Netherlands. Electronic address: eric.schoen@tno.nl.
LA  - eng
PT  - Journal Article
DEP - 20170711
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Aerosols)
RN  - 0 (Cytokines)
RN  - 789U1901C5 (Copper)
RN  - T8BEA5064F (cuprous oxide)
SB  - IM
MH  - Aerosols
MH  - Bronchi
MH  - Cell Survival/drug effects
MH  - Copper/*toxicity
MH  - Cytokines/genetics
MH  - Epithelial Cells
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Metal Nanoparticles/*toxicity
MH  - *Models, Biological
OTO - NOTNLM
OT  - Air-liquid interface
OT  - Analysis of variance
OT  - Copper oxide
OT  - Dose-response relation
OT  - Statistical design of experiments
EDAT- 2017/07/15 06:00
MHDA- 2018/05/10 06:00
CRDT- 2017/07/15 06:00
PHST- 2016/12/13 00:00 [received]
PHST- 2017/06/16 00:00 [revised]
PHST- 2017/07/07 00:00 [accepted]
PHST- 2017/07/15 06:00 [pubmed]
PHST- 2018/05/10 06:00 [medline]
PHST- 2017/07/15 06:00 [entrez]
AID - S0887-2333(17)30192-3 [pii]
AID - 10.1016/j.tiv.2017.07.006 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2017 Oct;44:339-348. doi: 10.1016/j.tiv.2017.07.006. Epub 2017 
      Jul 11.