ArticleFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association2020
Evaluation of pyrrolizidine alkaloid-induced genotoxicity using metabolically competent TK6 cell lines.
Article in Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Advancing genotoxicity assessment with transcriptomic biomarkers: from 2D to 3D HepaRG spheroid models.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- 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
- Evaluation of weak genotoxicity of hydroxychloroquine in human TK6 cells.Toxicology letters · 2024Article
- Revisiting the mutagenicity and genotoxicity of N-nitroso propranolol in bacterial and human in vitro assays.Regulatory toxicology and pharmacology : RTP · 2023Article
- Genotoxicity evaluation of nitrosamine impurities using human TK6 cells transduced with cytochrome P450s.Archives of toxicology · 2022Article
- Actein contributes to black cohosh extract-induced genotoxicity in human TK6 cells.Journal of applied toxicology : JAT · 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
- In vitro effects of cannabidiol and its main metabolites in mouse and human Sertoli cells.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
- The genotoxicity potential of luteolin is enhanced by CYP1A1 and CYP1A2 in human lymphoblastoid TK6 cells.Toxicology letters · 2021Article
- Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update.Archives of toxicology · 2021Review
- Identification of Pyrrolizidine Alkaloids inJournal of analytical methods in chemistry · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Pyrrolizidine alkaloid (PA)-containing plants are among the most common poisonous plants affecting humans, livestock, and wildlife worldwide. A large number of PAs are known to induce genetic damage after metabolic activation. In the present study, using a battery of fourteen newly developed TK6 cell lines, each expressing a single human cytochrome P450 (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C18, 2C9, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7), we identified specific CYPs responsible for bioactivating three PAs - lasiocarpine, riddelliine, and senkirkine. Among the fourteen cell lines, cells expressing CYP3A4 showed significant increases in PA-induced cytotoxicity, evidenced by decreased ATP production and cell viability, and increased caspase 3/7 activities. LC-MS/MS analysis revealed the formation of 1-hydroxymethyl-7-hydroxy-6,7-dihydropyrrolizine (DHP), the main reactive metabolite of PAs, in CYP3A4-expressing TK6 cells. DHP was also detected in CYP3A5- and 3A7-expressing cells after PA exposure, but to a much lesser extent. Subsequently, using a high-throughput micronucleus assay, we demonstrated that PAs induced concentration-dependent increases in micronuclei and G2/M phase cell cycle arrest in three CYP3A variant-expressing TK6 cell lines. Using Western blotting, we observed that PA-induced apoptosis, cell cycle changes, and DNA damage were primarily mediated by CYP3A4. Benchmark dose (BMD) modeling demonstrated that lasiocarpine, of the three PAs, was the most potent inducer of micronuclei, with a BMD
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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.