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• W2760350842 startingPage "662" @default.
• W2760350842 abstract "Regulatory in vitro genotoxicity testing exhibits shortcomings in specificity and mode of action (MoA) information. Thus, the aim of this work was to evaluate the performance of the novel MultiFlow® assay composed of mechanistic biomarkers quantified in TK6 cells after treatment (4 and 24 hr): γH2AX (DNA double strand breaks), phosphorylated H3 (mitotic cells), translocated p53 (genotoxicity), and cleaved PARP1 (apoptosis). A reference dataset of 31 compounds with well-established MoA was studied using the MicroFlow® micronucleus assay. A positive call was raised following the earlier published criteria from Litron Laboratories. In the light of our data, these evaluation criteria should probably be adjusted since only 8/11 (73%) nongenotoxicants and 18/20 (90%) genotoxicants were correctly identified. Moreover, there is a need for new in vitro tools to delineate the predominant MoA as in the MicroFlow® assay only 5/9 (56%) aneugens and 4/11 (36%) clastogens were correctly classified. In contrast, the MultiFlow® assay provides more in-depth information about the MoA and therefore reliably discriminates clastogens, aneugens, and nongenotoxicants. By using a lab-specific, practical threshold for the aforementioned biomarkers, 10/11 (91%) nongenotoxicants and 19/20 genotoxicants (95%), 9/11 (82%) clastogens, and 8/9 (89%) aneugens were correctly categorized, suggesting a clear improvement over the MicroFlow®. Furthermore, the MultiFlow markers were benchmarked against established methods to assess the validity of the data. Altogether, these findings demonstrated good agreement between the MultiFlow® assay and the benchmarking methods. Finally, p21 may improve class discrimination given the correct identification of 4/4 (100%) aneugens and 2/5 (40%) clastogens. Environ. Mol. Mutagen. 58:662–677, 2017. © 2017 Wiley Periodicals, Inc." @default.
• W2760350842 created "2017-10-06" @default.
• W2760350842 creator A5001185951 @default.
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• W2760350842 date "2017-09-21" @default.
• W2760350842 modified "2023-09-30" @default.
• W2760350842 title "Classification of in vitro genotoxicants using a novel multiplexed biomarker assay compared to the flow cytometric micronucleus test" @default.
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• W2760350842 doi "https://doi.org/10.1002/em.22130" @default.
• W2760350842 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28940655" @default.
• W2760350842 hasPublicationYear "2017" @default.
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