ArticleRegulatory toxicology and pharmacology : RTP2023
Revisiting the mutagenicity and genotoxicity of N-nitroso propranolol in bacterial and human in vitro assays.
Article in Regulatory toxicology and pharmacology : RTP, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Contribution of cytochrome P450-mediated metabolism to clavulanic acid-induced cytotoxicity in TK6-derived cytochrome P450-overexpressing cell lines.Scientific reports · 2026Article
- Nitrosamine Ames Data Review and Method Development: proceedings of a US FDA/HESI workshop.Mutagenesis · 2026Article
- Complex versus simpleScience advances · 2026Article
- Mutagenicity of EAT-positive NDSRIs in HepaRG spheroids.NAM journal · 2026Article
- Adjusting the Preincubation Conditions to Enhance the Ames Test for Detecting the Mutagenicity of N-Nitrosamines.Environmental and molecular mutagenesis · 2026Article
- Genotoxicity evaluation of ten nitrosamine drug substance-related impurities using 2D and 3D HepaRG cell models.Regulatory toxicology and pharmacology : RTP · 2025Article
- Alignment between Duplex Sequencing and transgenic rodent mutation assay data in the assessment of in vivo NDMA-induced mutagenesis.Archives of toxicology · 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
- Nitrosamine Drug Substance-Related Impurities (NDSRIs) in Pharmaceuticals: Formation, Mitigation Strategies, and Emphasis on Mutagenicity Risks.Pharmaceutical research · 2025Review
- An Enhanced Metabolization Protocol for In Vitro Genotoxicity Assessment of N-Nitrosamines in Mammalian Cells.Environmental and molecular mutagenesis · 2025Article
- Re-Evaluating Acceptable Intake: A Comparative Study of N-Nitrosomorpholine and N-Nitroso Reboxetine Potency.Environmental and molecular mutagenesis · 2025Article
- Escaping the cohort of concern: in vitro experimental evidence supports non-mutagenicity of N-nitroso-hydrochlorothiazide.Archives of toxicology · 2024Article
- Mutagenicity and genotoxicity evaluation of 15 nitrosamine drug substance-related impurities in human TK6 cells.Regulatory toxicology and pharmacology : RTP · 2024Article
- Optimizing the detection of N-nitrosamine mutagenicity in the Ames test.Regulatory toxicology and pharmacology : RTP · 2024Article
- Analytical Methodologies to Detect N-Nitrosamine Impurities in Active Pharmaceutical Ingredients, Drug Products and Other Matrices.Chemical research in toxicology · 2024Review
- Differential genotoxicity of Polygoni Multiflori in rat and human: insights from Ames test and S9 metabolic activation system.Scientific reports · 2024Article
- Metabolic activation of short-chain alkyl N-nitrosamines using Aroclor 1254 or phenobarbital/beta-naphthoflavone-induced rat or hamster S9 - A comparative analysis.Toxicology reports · 2024Article
- Evaluation of weak genotoxicity of hydroxychloroquine in human TK6 cells.Toxicology letters · 2024Article
- Application of HepaRG cells for genotoxicity assessment: a review.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2024Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Propranolol is a widely used β-blocker that can generate a nitrosated derivative, N-nitroso propranolol (NNP). NNP has been reported to be negative in the bacterial reverse mutation test (the Ames test) but genotoxic in other in vitro assays. In the current study, we systematically examined the in vitro mutagenicity and genotoxicity of NNP using several modifications of the Ames test known to affect the mutagenicity of nitrosamines, as well as a battery of genotoxicity tests using human cells. We found that NNP induced concentration-dependent mutations in the Ames test, both in two tester strains that detect base pair substitutions, TA1535 and TA100, as well as in the TA98 frameshift-detector strain. Although positive results were seen with rat liver S9, the hamster liver S9 fraction was more effective in bio-transforming NNP into a reactive mutagen. NNP also induced micronuclei and gene mutations in human lymphoblastoid TK6 cells in the presence of hamster liver S9. Using a panel of TK6 cell lines that each expresses a different human cytochrome P450 (CYP), CYP2C19 was identified as the most active enzyme in the bioactivation of NNP to a genotoxicant among those tested. NNP also induced concentration-dependent DNA strand breakage in metabolically competent 2-dimensional (2D) and 3D cultures of human HepaRG cells. This study indicates that NNP is genotoxic in a variety of bacterial and mammalian systems. Thus, NNP is a mutagenic and genotoxic nitrosamine and a potential human carcinogen.
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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.