PMID- 36558315
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221227
IS  - 2079-4991 (Print)
IS  - 2079-4991 (Electronic)
IS  - 2079-4991 (Linking)
VI  - 12
IP  - 24
DP  - 2022 Dec 15
TI  - Optimized High-Content Imaging Screening Quantifying Micronuclei Formation in 
      Polymer-Treated HaCaT Keratinocytes.
LID - 10.3390/nano12244463 [doi]
LID - 4463
AB  - Research on nano- and micro-plastic particles (NMPPs) suggests their potential 
      threat to human health. Some studies have even suggested genotoxic effects of 
      NMPP exposure, such as micronuclei (MN) formation, while others found the 
      opposite. To clarify the ability of NMPP to induce MN formation, we used 
      non-malignant HaCaT keratinocytes and exposed these to a variety of polystyrene 
      (PS) and poly methyl methacrylate (PMMA) particle types at different 
      concentrations and three different sizes. Investigations were performed following 
      acute (one day) and chronic exposure (five weeks) against cytotoxic 
      (amino-modified NMPPs) and genotoxic (methyl methanesulfonate, MMS) positive 
      controls. An optimized high-content imaging workflow was established strictly 
      according to OECD guidelines for analysis. Algorithm-based object segmentation 
      and MN identification led to computer-driven, unsupervised quantitative image 
      analysis results on MN frequencies among the different conditions and thousands 
      of cells per condition. This could only be realized using accutase, allowing for 
      partial cell detachment for optimal identification of bi-nucleated cells. 
      Cytotoxic amino-modified particles were not genotoxic; MMS was both. During acute 
      and long-term studies, PS and PMMA particles were neither toxic nor increased MN 
      formation, except for 1000 nm PS particles at the highest concentration of 
      unphysiological 100 microg/mL. Interestingly, ROS formation was significantly 
      decreased in this condition. Hence, most non-charged polymer particles were 
      neither toxic nor genotoxic, while aminated particles were toxic but not 
      genotoxic. Altogether, we present an optimized quantitative imaging workflow 
      applied to a timely research question in environmental toxicity.
FAU - Saadati, Fariba
AU  - Saadati F
AD  - ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 
      Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.
AD  - Clinic and Policlinic for Dermatology and Venereology, Rostock University Medical 
      Center, Strempelstr. 13, 18057 Rostock, Germany.
FAU - da Silva Brito, Walison Augusto
AU  - da Silva Brito WA
AUID- ORCID: 0000-0001-7215-7945
AD  - ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 
      Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.
AD  - Department of General Pathology, State University of Londrina, Rodovia Celso 
      Garcia Cid, Londrina 86057970, Brazil.
FAU - Emmert, Steffen
AU  - Emmert S
AUID- ORCID: 0000-0001-5630-4204
AD  - Clinic and Policlinic for Dermatology and Venereology, Rostock University Medical 
      Center, Strempelstr. 13, 18057 Rostock, Germany.
FAU - Bekeschus, Sander
AU  - Bekeschus S
AUID- ORCID: 0000-0002-8773-8862
AD  - ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 
      Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.
LA  - eng
GR  - 03Z22DN11/Federal Ministry of Education and Research/
GR  - 03Z22Di1/Federal Ministry of Education and Research/
GR  - 03Z22D511/Federal Ministry of Education and Research/
PT  - Journal Article
DEP - 20221215
PL  - Switzerland
TA  - Nanomaterials (Basel)
JT  - Nanomaterials (Basel, Switzerland)
JID - 101610216
PMC - PMC9788386
OTO - NOTNLM
OT  - Operetta CLS
OT  - algorithm
OT  - cytotoxicity
OT  - micro-plastic
OT  - nano-plastic
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/24 06:01
PMCR- 2022/12/15
CRDT- 2022/12/23 01:52
PHST- 2022/10/25 00:00 [received]
PHST- 2022/12/06 00:00 [revised]
PHST- 2022/12/09 00:00 [accepted]
PHST- 2022/12/23 01:52 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/24 06:01 [medline]
PHST- 2022/12/15 00:00 [pmc-release]
AID - nano12244463 [pii]
AID - nanomaterials-12-04463 [pii]
AID - 10.3390/nano12244463 [doi]
PST - epublish
SO  - Nanomaterials (Basel). 2022 Dec 15;12(24):4463. doi: 10.3390/nano12244463.