In vitro mammalian cell mutation assays based on transgenic reporters : A report of the International Workshop on Genotoxicity Testing (IWGT)
Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved..
Chemical safety evaluations require assessment of genetic toxicity. Transgenic rodent (TGR) assays permit enumeration of mutations in chromosomally-integrated targets contained in shuttle vectors. In order to improve in vitro mutagenicity assessment, and to substantially reduce animal use, in vitro assays using transgenic reporters have been developed. These assays are based on cells derived from TGRs, or cells transfected with transgenic shuttle vectors containing a mutation target. As part of the 7th International Workshop on Genotoxicity Testing, an In Vitro Mammalian Cell Gene Mutation Assay working group reviewed all published information pertaining to in vitro transgene mutagenicity assays; the utility, advantages and disadvantages of the assays were evaluated and discussed. The review revealed that over 20 TGR-based in vitro assays have been used to assess the mutagenic activity of over 150 agents. Overall, the Working Group considered in vitro transgene mutagenicity assays pragmatic tools for the safety evaluation of new and existing substances. A formal SWOT (strengths, weaknesses, opportunities, threats) analysis revealed advantages including the use of established scoring protocols, avoidance of laborious clone isolation and enumeration, ability to use metabolically competent primary cells, ability to detect different types of genetic damage, large dynamic range, and complementarity to in vivo TGR endpoints. Disadvantages include lack of validation and little consistency in protocols, the use of specialised reagents, the time and effort required for mutant enumeration, the use of some cell lines that lack metabolic capacity, and the need for multiple assays to cover all mutational mechanisms. Several assays have been partially validated, indicating promising reliability, reproducibility and applicability domain. Once in vitro transgene mutagenicity assays have been more thoroughly validated, they are well placed to augment or replace existing in vitro mammalian cell mutagenicity assays, particularly in cases where the in vivo TGR mutation assay is intended for follow-up.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:847 |
|---|---|
| Enthalten in: |
Mutation research. Genetic toxicology and environmental mutagenesis - 847(2019) vom: 19. Nov., Seite 403039 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
White, Paul A [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 12.03.2020 Date Revised 20.09.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.mrgentox.2019.04.002 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM303032693 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM303032693 | ||
| 003 | DE-627 | ||
| 005 | 20231225111958.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.mrgentox.2019.04.002 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1010.xml |
| 035 | |a (DE-627)NLM303032693 | ||
| 035 | |a (NLM)31699347 | ||
| 035 | |a (PII)S1383-5718(19)30006-3 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a White, Paul A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a In vitro mammalian cell mutation assays based on transgenic reporters |b A report of the International Workshop on Genotoxicity Testing (IWGT) |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.03.2020 | ||
| 500 | |a Date Revised 20.09.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Chemical safety evaluations require assessment of genetic toxicity. Transgenic rodent (TGR) assays permit enumeration of mutations in chromosomally-integrated targets contained in shuttle vectors. In order to improve in vitro mutagenicity assessment, and to substantially reduce animal use, in vitro assays using transgenic reporters have been developed. These assays are based on cells derived from TGRs, or cells transfected with transgenic shuttle vectors containing a mutation target. As part of the 7th International Workshop on Genotoxicity Testing, an In Vitro Mammalian Cell Gene Mutation Assay working group reviewed all published information pertaining to in vitro transgene mutagenicity assays; the utility, advantages and disadvantages of the assays were evaluated and discussed. The review revealed that over 20 TGR-based in vitro assays have been used to assess the mutagenic activity of over 150 agents. Overall, the Working Group considered in vitro transgene mutagenicity assays pragmatic tools for the safety evaluation of new and existing substances. A formal SWOT (strengths, weaknesses, opportunities, threats) analysis revealed advantages including the use of established scoring protocols, avoidance of laborious clone isolation and enumeration, ability to use metabolically competent primary cells, ability to detect different types of genetic damage, large dynamic range, and complementarity to in vivo TGR endpoints. Disadvantages include lack of validation and little consistency in protocols, the use of specialised reagents, the time and effort required for mutant enumeration, the use of some cell lines that lack metabolic capacity, and the need for multiple assays to cover all mutational mechanisms. Several assays have been partially validated, indicating promising reliability, reproducibility and applicability domain. Once in vitro transgene mutagenicity assays have been more thoroughly validated, they are well placed to augment or replace existing in vitro mammalian cell mutagenicity assays, particularly in cases where the in vivo TGR mutation assay is intended for follow-up | ||
| 650 | 4 | |a Consensus Development Conference | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a DNA damage | |
| 650 | 4 | |a Gene mutation | |
| 650 | 4 | |a Genotoxicity testing | |
| 650 | 4 | |a Mutagenicity | |
| 650 | 4 | |a Transgenic rodent | |
| 650 | 7 | |a Escherichia coli Proteins |2 NLM | |
| 650 | 7 | |a Pentosyltransferases |2 NLM | |
| 650 | 7 | |a EC 2.4.2.- |2 NLM | |
| 650 | 7 | |a Gpt protein, E coli |2 NLM | |
| 650 | 7 | |a EC 2.4.2.22 |2 NLM | |
| 700 | 1 | |a Luijten, Mirjam |e verfasserin |4 aut | |
| 700 | 1 | |a Mishima, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Cox, Julie A |e verfasserin |4 aut | |
| 700 | 1 | |a Hanna, Joleen N |e verfasserin |4 aut | |
| 700 | 1 | |a Maertens, Rebecca M |e verfasserin |4 aut | |
| 700 | 1 | |a Zwart, Edwin P |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Mutation research. Genetic toxicology and environmental mutagenesis |d 2013 |g 847(2019) vom: 19. Nov., Seite 403039 |w (DE-627)NLM230110533 |x 1879-3592 |7 nnns |
| 773 | 1 | 8 | |g volume:847 |g year:2019 |g day:19 |g month:11 |g pages:403039 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.mrgentox.2019.04.002 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 847 |j 2019 |b 19 |c 11 |h 403039 | ||