ArticleMutation research. Genetic toxicology and environmental mutagenesis2023
Error-corrected duplex sequencing enables direct detection and quantification of mutations in human TK6 cells with strong inter-laboratory consistency.
Article in Mutation research. Genetic toxicology and environmental mutagenesis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Application of error-corrected sequencing technologies for in vivo regulatory mutagenicity assessment.Regulatory toxicology and pharmacology : RTP · 2026Review
- Interpretation of in vitro concentration-response data for risk assessment and regulatory decision-making: Report from the 2022 IWGT quantitative analysis expert working group meeting.Environmental and molecular mutagenesis · 2025Review
- Transferability, Reproducibility and Sensitivity of Mutation Quantification by Duplex Sequencing.Environmental and molecular mutagenesis · 2025Article
- Whole genome mutagenicity evaluation using Hawk-Seq™ demonstrates high inter-laboratory reproducibility and concordance with the transgenic rodent gene mutation assay.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025Article
- Adverse Outcome Pathway-Informed Integrated Testing to Identify Chemicals Causing Genotoxicity Through Oxidative DNA Damage: Case Study on 4-Nitroquinoline 1-Oxide.Environmental and molecular mutagenesis · 2025Article
- MutSeqR: an open source R package for standardized analysis of error-corrected next-generation sequencing data in genetic toxicology.Bioinformatics advances · 2025Article
- Characterization of clonal dynamics using duplex sequencing in donor-recipient pairs decades after hematopoietic cell transplantation.Science translational medicine · 2024Article
- Effect of sequencing platforms on the sensitivity of chemical mutation detection using Hawk-Seq™.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2024Article
- CarcSeq detection of lorcaserin-induced clonal expansion of Pik3ca H1047R mutants in rat mammary tissue.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Evaluating the mutagenicity of N-nitrosodimethylamine in 2D and 3D HepaRG cell cultures using error-corrected next generation sequencing.Archives of toxicology · 2024Article
- Effects of urban-induced mutations on ecology, evolution and health.Nature ecology & evolution · 2024Review
- Adopting duplex sequencing technology for genetic toxicity testing: A proof-of-concept mutagenesis experiment with N-ethyl-N-nitrosourea (ENU)-exposed rats.Mutation research. Genetic toxicology and environmental mutagenesis · 2023Article
- Adopting Duplex Sequencing™ Technology for Genetic Toxicity Testing: A Proof-of-Concept Mutagenesis Experiment with N-Ethyl-N-Nitrosourea (ENU)-Exposed Rats.bioRxiv : the preprint server for biology · 2023Article
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16 authors.
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Abstract
Error-corrected duplex sequencing (DS) enables direct quantification of low-frequency mutations and offers tremendous potential for chemical mutagenicity assessment. We investigated the utility of DS to quantify induced mutation frequency (MF) and spectrum in human lymphoblastoid TK6 cells exposed to a prototypical DNA alkylating agent, N-ethyl-N-nitrosourea (ENU). Furthermore, we explored appropriate experimental parameters for this application, and assessed inter-laboratory reproducibility. In two independent experiments in two laboratories, TK6 cells were exposed to ENU (25-200 µM) and DNA was sequenced 48, 72, and 96 h post-exposure. A DS mutagenicity panel targeting twenty 2.4-kb regions distributed across the genome was used to sample diverse, genome-representative sequence contexts. A significant increase in MF that was unaffected by time was observed in both laboratories. Concentration-response in the MF from the two laboratories was strongly positively correlated (r = 0.97). C:G>T:A, T:A>C:G, T:A>A:T, and T:A>G:C mutations increased in consistent, concentration-dependent manners in both laboratories, with high proportions of C:G>T:A at all time points. The consistent results across the three time points suggest that 48 h may be sufficient for mutation analysis post-exposure. The target sites responded similarly between the two laboratories and revealed a higher average MF in intergenic regions. These results, demonstrating remarkable reproducibility across time and laboratory for both MF and spectrum, support the high value of DS for characterizing chemical mutagenicity in both research and regulatory evaluation.
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