ArticleScientific reports2024
Differential genotoxicity of Polygoni Multiflori in rat and human: insights from Ames test and S9 metabolic activation system.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Preliminary Assessment of Mutagenicity and In Vivo Toxicity of Date Pit Ethanolic Extracts: Safety Screening for Circular Economy Applications.Foods (Basel, Switzerland) · 2026Article
- Preliminary Genotoxicity Assessment of Calcium Phosphate Cement Incorporated with Palm Tocotrienol Using Bacterial Reverse Mutation Assay.Biomedicines · 2026Article
- High-Throughput Testing for Unknown Mutagens and Cytotoxica via Duplex Planar Ames-Cytotoxicity Bioassay Including Metabolic S9 Activation.Analytical chemistry · 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
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Authors and funding
15 authors.
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Abstract
The Ames test is used worldwide to initially screen the mutagenic potential of new chemicals. In the standard Ames test, S. typhimurium strains (TA100, TA98, TA1535, and TA1537) and Escherichia coli (WP2uvrA) are treated with substances with/without cytochrome P450s (CYPs)-induced rat S9 fractions for identifying mutagens and pro-mutagens. However, many substances show completely different toxicity patterns depending on whether the liver S9 fraction belongs to rats or humans. The natural product Polygoni Multiflori Radix (PMR) can also show bacterial reverse mutation, followed by the rat or human liver S9 fraction. While PMR elicits reverse mutations in the TA1537 strain in rat liver S9 but not in human liver S9, this mechanism has not been verified yet. To explain this, the differences in metabolic enzymes compositions commonly observed between rats and humans have been implicated. This study aimed to explore the key factors that cause differences in the genotoxicity of PMR between rat and human liver S9 metabolic enzymes. The results of next-generation sequencing (NGS) analysis showed that both rat and human metabolic enzymes caused similar mutations in TA1537. However, when the metabolic enzymes in each S9 fraction were analyzed using ion mobility tandem mass spectrometry (IM-MS), rat- and human-specific enzymes were identified among the cytochrome (CYP) family, especially aryl hydrocarbon receptor (AHR)-related CYPs. These findings suggest that CYP1A1 isoforms contribute to the mechanism of PMR in the Ames test. Therefore, an in vitro Ames test might be more reliable in predicting genotoxicity for both rodents and humans. This will also help overcome the limitations of laboratory animal-based toxicity evaluations, which provide unreliable results due to interspecies differences between humans and rodents.
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