PMID- 32347014
OWN - NLM
STAT- MEDLINE
DCOM- 20210517
LR  - 20210517
IS  - 1613-6829 (Electronic)
IS  - 1613-6810 (Linking)
VI  - 16
IP  - 36
DP  - 2020 Sep
TI  - 21st Century Tools for Nanotoxicology: Transcriptomic Biomarker Panel and 
      Precision-Cut Lung Slice Organ Mimic System for the Assessment of 
      Nanomaterial-Induced Lung Fibrosis.
PG  - e2000272
LID - 10.1002/smll.202000272 [doi]
AB  - There is an urgent need for reliable toxicity assays to support the human health 
      risk assessment of an ever increasing number of engineered nanomaterials (ENMs). 
      Animal testing is not a suitable option for ENMs. Sensitive in vitro models and 
      mechanism-based targeted in vitro assays that enable accurate prediction of in 
      vivo responses are not yet available. In this proof-of-principle study, publicly 
      available mouse lung transcriptomics data from studies investigating 
      xenobiotic-induced lung diseases are used and a 17-gene biomarker panel (PFS17) 
      applicable to the assessment of lung fibrosis is developed. The PFS17 is 
      validated using a limited number of in vivo mouse lung transcriptomics datasets 
      from studies investigating ENM-induced responses. In addition, an ex vivo 
      precision-cut lung slice (PCLS) model is optimized for screening of potentially 
      inflammogenic and pro-fibrotic ENMs. Using bleomycin and a multiwalled carbon 
      nanotube, the practical application of the PCLS method as a sensitive alternative 
      to whole animal tests to screen ENMs that may potentially induce inhalation 
      toxicity is shown. Conditional to further optimization and validation, it is 
      established that a combination of PFS17 and the ex vivo PCLS method will serve as 
      a robust and sensitive approach to assess lung inflammation and fibrosis induced 
      by ENMs.
CI  - (c) 2020 Her Majesty the Queen in Right of Canada. Published by Wiley-VCH Verlag 
      GmbH & Co. KGaA. Reproduced with the permission of the Minister of Health Canada.
FAU - Rahman, Luna
AU  - Rahman L
AD  - Environmental Health Science and Research Bureau, Health Canada, Sir Frederick G 
      Banting Research Centre, 251 Sir Frederick Banting Driveway, Building 22, Ottawa, 
      ON, K1A 0K9, Canada.
FAU - Williams, Andrew
AU  - Williams A
AD  - Environmental Health Science and Research Bureau, Health Canada, Sir Frederick G 
      Banting Research Centre, 251 Sir Frederick Banting Driveway, Building 22, Ottawa, 
      ON, K1A 0K9, Canada.
FAU - Gelda, Krishna
AU  - Gelda K
AD  - Environmental Health Science and Research Bureau, Health Canada, Sir Frederick G 
      Banting Research Centre, 251 Sir Frederick Banting Driveway, Building 22, Ottawa, 
      ON, K1A 0K9, Canada.
FAU - Nikota, Jake
AU  - Nikota J
AD  - Environmental Health Science and Research Bureau, Health Canada, Sir Frederick G 
      Banting Research Centre, 251 Sir Frederick Banting Driveway, Building 22, Ottawa, 
      ON, K1A 0K9, Canada.
FAU - Wu, Dongmei
AU  - Wu D
AD  - Environmental Health Science and Research Bureau, Health Canada, Sir Frederick G 
      Banting Research Centre, 251 Sir Frederick Banting Driveway, Building 22, Ottawa, 
      ON, K1A 0K9, Canada.
FAU - Vogel, Ulla
AU  - Vogel U
AD  - National Research Centre for the Working Environment, Lerso Parkalle 105, 
      Copenhagen, 2100, Denmark.
AD  - Department of Micro- and Nanotechnology, Technical University of Denmark, 
      Building 101A 2800 Copenhagen, Lyngby, Denmark.
FAU - Halappanavar, Sabina
AU  - Halappanavar S
AUID- ORCID: 0000-0001-6283-237X
AD  - Environmental Health Science and Research Bureau, Health Canada, Sir Frederick G 
      Banting Research Centre, 251 Sir Frederick Banting Driveway, Building 22, Ottawa, 
      ON, K1A 0K9, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200429
PL  - Germany
TA  - Small
JT  - Small (Weinheim an der Bergstrasse, Germany)
JID - 101235338
RN  - 0 (Biomarkers)
SB  - IM
MH  - Animals
MH  - *Biomarkers/analysis
MH  - *Gene Expression Profiling/methods/standards
MH  - Lung/drug effects/physiopathology
MH  - Mice
MH  - *Nanostructures/toxicity
MH  - *Pulmonary Fibrosis/chemically induced/diagnosis/genetics/physiopathology
MH  - *Toxicology/methods/trends
MH  - Transcriptome
OTO - NOTNLM
OT  - advanced lung exposure models
OT  - bi-clustering
OT  - fibrosis
OT  - lung pathology
OT  - organoid culture
OT  - predictive gene signature
EDAT- 2020/04/30 06:00
MHDA- 2021/05/18 06:00
CRDT- 2020/04/30 06:00
PHST- 2020/01/14 00:00 [received]
PHST- 2020/03/23 00:00 [revised]
PHST- 2020/03/24 00:00 [accepted]
PHST- 2020/04/30 06:00 [pubmed]
PHST- 2021/05/18 06:00 [medline]
PHST- 2020/04/30 06:00 [entrez]
AID - 10.1002/smll.202000272 [doi]
PST - ppublish
SO  - Small. 2020 Sep;16(36):e2000272. doi: 10.1002/smll.202000272. Epub 2020 Apr 29.