The in vitro transgenic rodent assay in primary MutaMouse hepatocytes compared to the mammalian cell gene mutation assay using the HPRT gene

The in vitro transgenic rodent assay in primary MutaMouse hepatocytes compared to the mammalian cell gene mutation assay using the HPRT gene | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Environmental and Molecular Mutagenesis This is a preprint and has not been peer reviewed. Data may be preliminary. 11 August 2025 V1 Latest version Share on The in vitro transgenic rodent assay in primary MutaMouse hepatocytes compared to the mammalian cell gene mutation assay using the HPRT gene Authors : Alina Goepfert , Kylee Ronnenberg , Claudia Ruelker , Silke Spang , Naveed Honarvar [email protected] , and Robert Landsiedel Authors Info & Affiliations https://doi.org/10.22541/au.175492806.67683575/v1 Published Environmental and Molecular Mutagenesis Version of record Peer review timeline 228 views 138 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Gene mutations can be detected in mammalian cells in vitro using indicator genes like the hypoxanthine-guanine-phosphoribosyltransferase (HPRT) gene. These assays have been adopted as OECD test guidelines (TG, e.g. OECD TG no. 476) and are used for regulatory purposes. The in vitro transgenic rodent assay (TGRA), typically performed in primary MutaMouse hepatocytes, is a novel approach for the detection and quantification of gene mutations. Its performance resembles the in vivo TGRA, an in vivo gene mutation assay that has been adopted as OECD TG (no. 488). Although the potential of the in vitro TGRA to identify mutagens has been reported, the performance of this assay as compared to an established in vitro gene mutation assay has not been reported. This study compared the in vitro TGRA with the HPRT assay using ten known in vivo mutagens. The in vitro TGRA correctly identified all ten mutagens, whereas the HPRT assay identified only nine. Benchmark concentration (BMC) modelling for the nine substances detected by both assays revealed overlapping confidence intervals for six compounds, indicating comparable sensitivity. For three mutagens, the HPRT assay yielded lower BMC intervals. Additionally, eight substances known to be non-mutagenic in vivo were tested in the in vitro TGRA, where applicable up to cytotoxic concentrations. While cytotoxicity did not induce increased mutant frequencies, it reduced DNA yield, impairing mutagenicity assessment. The results of this study add to the information on the sensitivity and robustness of the in vitro TGRA and provide essential information for the validation of the assay. Supplementary Material File (tgrvitro_hprt_final_11aug2025.docx) Download 369.47 KB Information & Authors Information Version history V1 Version 1 11 August 2025 Peer review timeline Published Environmental and Molecular Mutagenesis Version of Record 29 Oct 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Collection Environmental and Molecular Mutagenesis Keywords benchmark concentration modelling gene mutation gentlemacs liver perfusion validation Authors Affiliations Alina Goepfert BASF SE View all articles by this author Kylee Ronnenberg BASF SE View all articles by this author Claudia Ruelker BASF SE View all articles by this author Silke Spang BASF SE View all articles by this author Naveed Honarvar [email protected] BASF SE View all articles by this author Robert Landsiedel BASF SE View all articles by this author Metrics & Citations Metrics Article Usage 228 views 138 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Alina Goepfert, Kylee Ronnenberg, Claudia Ruelker, et al. The in vitro transgenic rodent assay in primary MutaMouse hepatocytes compared to the mammalian cell gene mutation assay using the HPRT gene. Authorea . 11 August 2025. 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