ArticleBMC genomics2015
Characterizing Benzo[a]pyrene-induced lacZ mutation spectrum in transgenic mice using next-generation sequencing.
Article in BMC genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Benchmark Response Values for Error-Corrected Sequencing Mutagenicity Assessment Technologies.Environmental and molecular mutagenesis · 2026Article
- 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
- MutSeqR: an open source R package for standardized analysis of error-corrected next-generation sequencing data in genetic toxicology.Bioinformatics advances · 2025Article
- Utilizing biological experimental data and molecular dynamics for the classification of mutational hotspots through machine learning.Bioinformatics advances · 2024Article
- The functional mutational landscape of theiScience · 2023Article
- Duplex sequencing identifies genomic features that determine susceptibility to benzo(a)pyrene-induced in vivo mutations.BMC genomics · 2022Article
- New homozygous gpt delta transgenic rat strain improves an efficiency of the in vivo mutagenicity assay.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Article
- The 28 + 28 day design is an effective sampling time for analyzing mutant frequencies in rapidly proliferating tissues of MutaMouse animals.Archives of toxicology · 2021Article
- Direct quantification of in vivo mutagenesis and carcinogenesis using duplex sequencing.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Chemically induced mutations in a MutaMouse reporter gene inform mechanisms underlying human cancer mutational signatures.Communications biology · 2020Article
- Next-Generation Genotoxicology: Using Modern Sequencing Technologies to Assess Somatic Mutagenesis and Cancer Risk.Environmental and molecular mutagenesis · 2020Review
- Whole Genome Sequencing of the Mutamouse Model Reveals Strain- and Colony-Level Variation, and Genomic Features of the Transgene Integration Site.Scientific reports · 2019Article
- Integrated In Vivo Genotoxicity Assessment of Procarbazine Hydrochloride Demonstrates Induction of Pig-a and LacZ Mutations, and Micronuclei, in MutaMouse Hematopoietic Cells.Environmental and molecular mutagenesis · 2019Article
- In Utero Exposure to Benzo[a]pyrene Induces Ovarian Mutations at Doses That Deplete Ovarian Follicles in Mice.Environmental and molecular mutagenesis · 2019Article
- Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring.Communications biology · 2019Article
- A model for RAS mutation patterns in cancers: finding the sweet spot.Nature reviews. Cancer · 2018Review
- Mutation Analysis in Cultured Cells of Transgenic Rodents.International journal of molecular sciences · 2018Article
- Mutagenic Replication of NChemical research in toxicology · 2017Article
- Evaluation of in vivo mutagenesis for assessing the health risk of air pollutants.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe transgenic rodent mutation reporter assay provides an efficient approach to identify mutagenic agents in vivo. A major advantage of this assay is that mutant reporter transgenes can be sequenced to provide information on the mode of action of a mutagen and to identify clonally expanded mutations. However, conventional DNA sequence analysis is laborious and expensive for long transgenes, such as lacZ (3096 bp), and is not normally implemented in routine screening.
methodsWe developed a high-throughput next-generation sequencing (NGS) approach to simultaneously sequence large numbers of barcoded mutant lacZ transgenes from different animals. We collected 3872 mutants derived from the bone marrow DNA of six Muta™Mouse males exposed to the well-established mutagen benzo[a]pyrene (BaP) and six solvent-exposed controls. Mutants within animal samples were pooled, barcoded, and then sequenced using NGS.
resultsWe identified 1652 mutant sequences from 1006 independent mutations that underwent clonal expansion. This deep sequencing analysis of mutation spectrum demonstrated that BaP causes primarily guanine transversions (e.g. G:C → T:A), which is highly consistent with previous studies employing Sanger sequencing. Furthermore, we identified novel mutational hotspots in the lacZ transgene that were previously uncharacterized by Sanger sequencing. Deep sequencing also allowed for an unprecedented ability to correct for clonal expansion events, improving the sensitivity of the mutation reporter assay by 50 %.
conclusionThese results demonstrate that the high-throughput nature and reduced costs offered by NGS provide a sensitive and fast approach for elucidating and comparing mutagenic mechanisms of various agents among tissues and enabling improved evaluation of genotoxins.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.