PMID- 37713377
OWN - NLM
STAT- MEDLINE
DCOM- 20230918
LR  - 20230919
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 18
IP  - 9
DP  - 2023
TI  - Nanomaterial genotoxicity evaluation using the high-throughput p53-binding 
      protein 1 (53BP1) assay.
PG  - e0288737
LID - 10.1371/journal.pone.0288737 [doi]
LID - e0288737
AB  - Toxicity evaluation of engineered nanomaterials is challenging due to the ever 
      increasing number of materials and because nanomaterials (NMs) frequently 
      interfere with commonly used assays. Hence, there is a need for robust, 
      high-throughput assays with which to assess their hazard potential. The present 
      study aimed at evaluating the applicability of a genotoxicity assay based on the 
      immunostaining and foci counting of the DNA repair protein 53BP1 (p53-binding 
      protein 1), in a high-throughput format, for NM genotoxicity assessment. For 
      benchmarking purposes, we first applied the assay to a set of eight known 
      genotoxic agents, as well as X-ray irradiation (1 Gy). Then, a panel of NMs and 
      nanobiomaterials (NBMs) was evaluated with respect to their impact on cell 
      viability and genotoxicity, and to their potential to induce reactive oxygen 
      species (ROS) production. The genotoxicity recorded using the 53BP1 assay was 
      confirmed using the micronucleus assay, also scored via automated 
      (high-throughput) microscopy. The 53BP1 assay successfully identified genotoxic 
      compounds on the HCT116 human intestinal cell line. None of the tested NMs showed 
      any genotoxicity using the 53BP1 assay, except the positive control consisting in 
      (CoO)(NiO) NMs, while only TiO2 NMs showed positive outcome in the micronucleus 
      assay. Only Fe3O4 NMs caused significant elevation of ROS, not correlated to DNA 
      damage. Therefore, owing to its adequate predictivity of the genotoxicity of most 
      of the tested benchmark substance and its ease of implementation in a high 
      throughput format, the 53BP1 assay could be proposed as a complementary 
      high-throughput screening genotoxicity assay, in the context of the development 
      of New Approach Methodologies.
CI  - Copyright: (c) 2023 Fontaine et al. This is an open access article distributed 
      under the terms of the Creative Commons Attribution License, which permits 
      unrestricted use, distribution, and reproduction in any medium, provided the 
      original author and source are credited.
FAU - Fontaine, Maelle
AU  - Fontaine M
AD  - CEA, CNRS, IRIG, SyMMES-CIBEST, Univ. Grenoble Alpes, Grenoble, France.
FAU - Bartolami, Eline
AU  - Bartolami E
AD  - CEA, CNRS, IRIG, SyMMES-CIBEST, Univ. Grenoble Alpes, Grenoble, France.
FAU - Prono, Marion
AU  - Prono M
AD  - CEA, CNRS, IRIG, SyMMES-CIBEST, Univ. Grenoble Alpes, Grenoble, France.
FAU - Beal, David
AU  - Beal D
AD  - CEA, CNRS, IRIG, SyMMES-CIBEST, Univ. Grenoble Alpes, Grenoble, France.
FAU - Blosi, Magda
AU  - Blosi M
AD  - National Research Council, Institute of Science, Technology and Sustainability 
      for Ceramic Materials ISSMC-CNR (Former ISTEC-CNR), Faenza, Italy.
FAU - Costa, Anna L
AU  - Costa AL
AD  - National Research Council, Institute of Science, Technology and Sustainability 
      for Ceramic Materials ISSMC-CNR (Former ISTEC-CNR), Faenza, Italy.
FAU - Ravagli, Costanza
AU  - Ravagli C
AD  - Ce.Ri.Col, Colorobbia Consulting S.R.L, Sovigliana-Vinci, Firenze, Italy.
FAU - Baldi, Giovanni
AU  - Baldi G
AD  - Ce.Ri.Col, Colorobbia Consulting S.R.L, Sovigliana-Vinci, Firenze, Italy.
FAU - Sprio, Simone
AU  - Sprio S
AD  - National Research Council, Institute of Science, Technology and Sustainability 
      for Ceramic Materials ISSMC-CNR (Former ISTEC-CNR), Faenza, Italy.
FAU - Tampieri, Anna
AU  - Tampieri A
AD  - National Research Council, Institute of Science, Technology and Sustainability 
      for Ceramic Materials ISSMC-CNR (Former ISTEC-CNR), Faenza, Italy.
FAU - Fenoglio, Ivana
AU  - Fenoglio I
AD  - Department of Chemistry, University of Turin, Turin, Italy.
FAU - Tran, Lang
AU  - Tran L
AD  - Institute of Occupational Medicine, Edinburgh, Midlothian, United Kingdom.
FAU - Fadeel, Bengt
AU  - Fadeel B
AD  - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Carriere, Marie
AU  - Carriere M
AD  - CEA, CNRS, IRIG, SyMMES-CIBEST, Univ. Grenoble Alpes, Grenoble, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230915
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Humans
MH  - Reactive Oxygen Species
MH  - *Tumor Suppressor Protein p53
MH  - Benchmarking
MH  - DNA Damage
MH  - *Nanostructures
PMC - PMC10503773
COIS- The authors have declared that no competing interests exist.
EDAT- 2023/09/15 18:42
MHDA- 2023/09/18 12:44
PMCR- 2023/09/15
CRDT- 2023/09/15 13:33
PHST- 2023/03/02 00:00 [received]
PHST- 2023/07/04 00:00 [accepted]
PHST- 2023/09/18 12:44 [medline]
PHST- 2023/09/15 18:42 [pubmed]
PHST- 2023/09/15 13:33 [entrez]
PHST- 2023/09/15 00:00 [pmc-release]
AID - PONE-D-23-06165 [pii]
AID - 10.1371/journal.pone.0288737 [doi]
PST - epublish
SO  - PLoS One. 2023 Sep 15;18(9):e0288737. doi: 10.1371/journal.pone.0288737. 
      eCollection 2023.