ArticleToxicological sciences : an official journal of the Society of Toxicology2020
Development and Application of TK6-derived Cells Expressing Human Cytochrome P450s for Genotoxicity Testing.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Optimization of Cytokinesis-Block Micronucleus Assay for Clastogenic Risk Assessment of Silver-Containing Nanomaterials.Nanomaterials (Basel, Switzerland) · 2026Article
- Genotoxic Potential of Metodesnitazene and Etodesnitazene: Insights with and Without S9 Metabolic Activation.International journal of molecular sciences · 2026Article
- Development of a DNA damage assay system using stable human hepatocytes.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2026Article
- Genotoxicity evaluation of ten nitrosamine drug substance-related impurities using 2D and 3D HepaRG cell models.Regulatory toxicology and pharmacology : RTP · 2025Article
- Development of a TK6-derived cell line expressing four human cytochrome P450s for genotoxicity testing.Toxicology in vitro : an international journal published in association with BIBRA · 2025Article
- Mutagenicity and genotoxicity evaluation of 15 nitrosamine drug substance-related impurities in human TK6 cells.Regulatory toxicology and pharmacology : RTP · 2024Article
- Toxicity of cannabidiol and its metabolites in TM3 mouse Leydig cells: a comparison with primary human Leydig cells.Archives 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
- Revisiting the mutagenicity and genotoxicity of N-nitroso propranolol in bacterial and human in vitro assays.Regulatory toxicology and pharmacology : RTP · 2023Article
- Article
- Genotoxicity evaluation of nitrosamine impurities using human TK6 cells transduced with cytochrome P450s.Archives of toxicology · 2022Article
- Nicotine Inhibits the Cytotoxicity and Genotoxicity of NNK Mediated by CYP2A13 in BEAS-2B Cells.Molecules (Basel, Switzerland) · 2022Article
- The expression of Phase II drug-metabolizing enzymes in human B-lymphoblastoid TK6 cells.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2022Article
- Cell survival after DNA damage in the comet assay.Archives of toxicology · 2021Article
- The genotoxicity potential of luteolin is enhanced by CYP1A1 and CYP1A2 in human lymphoblastoid TK6 cells.Toxicology letters · 2021Article
- Novel Psychoactive Phenethylamines: Impact on Genetic Material.International journal of molecular sciences · 2020Article
- Performance of HepaRG and HepG2 cells in the high-throughput micronucleus assay for in vitro genotoxicity assessment.Journal of toxicology and environmental health. Part A · 2020Article
- Evaluation of pyrrolizidine alkaloid-induced genotoxicity using metabolically competent TK6 cell lines.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolism plays a key role in chemical genotoxicity; however, most mammalian cells used for in vitro genotoxicity testing lack effective metabolizing enzymes. We recently developed a battery of TK6-derived cell lines that individually overexpress 1 of 8 cytochrome P450s (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, and 3A4) using a lentiviral expression system. The increased expression and metabolic function of each individual CYP in each established cell line were confirmed using real-time PCR, Western blotting, and mass spectrometry analysis; the parental TK6 cells and empty vector (EV) transduced cells had negligible CYP levels. Subsequently, we evaluated these cell lines using 2 prototypical polyaromatic hydrocarbon mutagens, 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P), that require metabolic activation to exert their genotoxicity. DMBA-induced cytotoxicity, phosphorylation of histone H2A.X, and micronucleus formation were significantly increased in TK6 cells with CYP1A1, 1B1, 2B6, and 2C19 expression as compared with EV controls. B[a]P significantly increased cytotoxicity, DNA damage, and chromosomal damage in TK6 cells overexpressing CYP1A1 and 1B1 when compared with EV controls. B[a]P also induced micronucleus formation in TK6 cells expressing CYP1A2. These results suggest that our CYP-expressing TK6 cell system can be used to detect the genotoxicity of compounds requiring metabolic transformation.
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