{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T18:09:09Z","timestamp":1773511749560,"version":"3.50.1"},"reference-count":83,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T00:00:00Z","timestamp":1457049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["NIEHS 1R01ES020750"],"award-info":[{"award-number":["NIEHS 1R01ES020750"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Health Canada Genomics Research and Development Initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p><jats:italic>In vitro<\/jats:italic> transcriptional signatures that predict toxicities can facilitate chemical screening. We previously developed a transcriptomic biomarker (known as TGx\u201028.65) for classifying agents as genotoxic (DNA damaging) and non\u2010genotoxic in human lymphoblastoid TK6 cells. Because TK6 cells do not express cytochrome P450s, we confirmed accurate classification by the biomarker in cells co\u2010exposed to 1% 5,6 benzoflavone\/phenobarbital\u2010induced rat liver S9 for metabolic activation. However, chemicals may require different types of S9 for activation. Here we investigated the response of TK6 cells to higher percentages of Aroclor\u2010, benzoflavone\/phenobarbital\u2010, or ethanol\u2010induced rat liver S9 to expand TGx\u201028.65 biomarker applicability. Transcriptional profiles were derived 3 to 4 hr following a 4 hr co\u2010exposure of TK6 cells to test chemicals and S9. Preliminary studies established that 10% Aroclor\u2010 and 5% ethanol\u2010induced S9 alone did not induce the TGx\u201028.65 biomarker genes. Seven genotoxic and two non\u2010genotoxic chemicals (and concurrent solvent and positive controls) were then tested with one of the S9s (selected based on cell survival and micronucleus induction). Relative survival and micronucleus frequency was assessed by flow cytometry in cells 20 hr post\u2010exposure. Genotoxic\/non\u2010genotoxic chemicals were accurately classified using the different S9s. One technical replicate of cells co\u2010treated with dexamethasone and 10% Aroclor\u2010induced S9 was falsely classified as genotoxic, suggesting caution in using high S9 concentrations. Even low concentrations of genotoxic chemicals (those not causing cytotoxicity) were correctly classified, demonstrating that TGx\u201028.65 is a sensitive biomarker of genotoxicity. A meta\u2010analysis of datasets from 13 chemicals supports that different S9s can be used in TK6 cells, without impairing classification using the TGx\u201028.65 biomarker. Environ. Mol. Mutagen. 57:243\u2013260, 2016. \u00a9 2016 Her Majesty the Queen in Right of Canada. 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