A comparison of transgenic rodent mutation and in vivo comet assay responses for 91 chemicals.

Autor: Kirkland D; Kirkland Consulting, PO Box 79, Tadcaster LS24 0AS, UK., Levy DD; US Food and Drug Administration Center for Food Safety and Applied Nutrition, College Park, MD, USA., LeBaron MJ; The Dow Chemical Company, Toxicology & Environmental Research & Consulting, Midland, MI, USA., Aardema MJ; Marilyn Aardema Consulting LLC, 5315 Oakbrook Dr., Fairfield, OH 45014, USA., Beevers C; Exponent International Ltd, Harrogate, UK., Bhalli J; MilliporeSigma, BioReliance Toxicology Testing Services, Rockville, MD, USA., Douglas GR; Environmental Health Science and Research Bureau, Health Canada, Ottawa, K1A 0K9, Canada., Escobar PA; Merck & Co. Inc., West Point, PA 19486, USA., Farabaugh CS; Charles River Laboratories, Skokie, IL, USA., Guerard M; Roche Innovation Center Basel, pRed, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Johnson GE; Swansea University Medical School, Swansea, UK., Kulkarni R; MilliporeSigma, BioReliance Toxicology Testing Services, Rockville, MD, USA., Le Curieux F; European Chemicals Agency, Helsinki, Finland., Long AS; Environmental Health Science and Research Bureau, Health Canada, Ottawa, K1A 0K9, Canada., Lott J; Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany., Lovell DP; St George's Medical School, University of London, London, UK., Luijten M; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands., Marchetti F; Environmental Health Science and Research Bureau, Health Canada, Ottawa, K1A 0K9, Canada., Nicolette JJ; AbbVie, Inc., Pre-clinical Safety, North Chicago, Illinois, USA., Pfuhler S; Procter & Gamble, Global Product Stewardship, Mason, OH 45040, USA., Roberts DJ; Charles River Laboratories, Skokie, IL, USA., Stankowski LF Jr; Charles River Laboratories, Skokie, IL, USA., Thybaud V; Sanofi, Vitry-sur-Seine, France., Weiner SK; Janssen Research & Development, Spring House, PA 19477, USA., Williams A; Environmental Health Science and Research Bureau, Health Canada, Ottawa, K1A 0K9, Canada., Witt KL; National Institute of Environmental Health Sciences/Division of the National Toxicology Program, Research Triangle Park, NC, USA., Young R; MilliporeSigma, BioReliance Toxicology Testing Services, Rockville, MD, USA.
Jazyk: angličtina
Zdroj: Mutation research. Genetic toxicology and environmental mutagenesis [Mutat Res Genet Toxicol Environ Mutagen] 2019 Mar; Vol. 839, pp. 21-35. Date of Electronic Publication: 2019 Jan 18.
DOI: 10.1016/j.mrgentox.2019.01.007
Abstrakt: A database of 91 chemicals with published data from both transgenic rodent mutation (TGR) and rodent comet assays has been compiled. The objective was to compare the sensitivity of the two assays for detecting genotoxicity. Critical aspects of study design and results were tabulated for each dataset. There were fewer datasets from rats than mice, particularly for the TGR assay, and therefore, results from both species were combined for further analysis. TGR and comet responses were compared in liver and bone marrow (the most commonly studied tissues), and in stomach and colon evaluated either separately or in combination with other GI tract segments. Overall positive, negative, or equivocal test results were assessed for each chemical across the tissues examined in the TGR and comet assays using two approaches: 1) overall calls based on weight of evidence (WoE) and expert judgement, and 2) curation of the data based on a priori acceptability criteria prior to deriving final tissue specific calls. Since the database contains a high prevalence of positive results, overall agreement between the assays was determined using statistics adjusted for prevalence (using AC1 and PABAK). These coefficients showed fair or moderate to good agreement for liver and the GI tract (predominantly stomach and colon data) using WoE, reduced agreement for stomach and colon evaluated separately using data curation, and poor or no agreement for bone marrow using both the WoE and data curation approaches. Confidence in these results is higher for liver than for the other tissues, for which there were less data. Our analysis finds that comet and TGR generally identify the same compounds (mainly potent mutagens) as genotoxic in liver, stomach and colon, but not in bone marrow. However, the current database content precluded drawing assay concordance conclusions for weak mutagens and non-DNA reactive chemicals.
(Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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