Publications by authors named "N Koyama"
There is growing recognition across broad sectors of the toxicology community that gene expression biomarkers have the potential to identify genotoxic and nongenotoxic carcinogens through a weight-of-evidence approach, providing opportunities to reduce reliance on the 2-year bioassay to identify carcinogens. In August 2022, a workshop within the International Workshops on Genotoxicity Testing (IWGT) was held to critically review current methods to identify genotoxicants using various 'omics profiling methods. Here, we describe the findings of a workshop subgroup focused on the state of the science regarding the use of biomarkers to identify chemicals that act as genotoxicants in vivo.
View Article and Find Full Text PDFArticle Synopsis
- Gene expression biomarkers can help identify both genotoxic and non-genotoxic carcinogens, which could reduce the need for animal testing.
- In August 2022, a workshop reviewed current methods for using transcriptomic profiling to detect genotoxic chemicals, examining 1341 papers to find reliable biomarkers.
- The analysis identified two promising in vivo biomarkers and three in vitro biomarkers that show over 92% predictive accuracy and can be adapted for various testing conditions, with support from workshop participants for their regulatory adoption.
Article Synopsis
- In human health risk assessment, genotoxicity hazards of chemicals typically start with a set of in vitro tests, but these tests don't capture all potential genotoxic endpoints, leading to sometimes contradictory results.
- Mathematical modeling can improve the interpretation of these tests by accounting for each test's strengths and weaknesses, providing objective predictions with associated uncertainties.
- A study found that combining a mammalian in vitro clastogenicity test and a gene mutation test offers strong evidence for genotoxic hazard assessment, but the bacterial reverse mutation (Ames) test alone can still provide useful evidence when no other data is available.
Background: Primary aromatic amines (PAAs) present significant challenges in the prediction of mutagenicity using current standard quantitative structure activity relationship (QSAR) systems, which are knowledge-based and statistics-based, because of their low positive prediction values (PPVs). Previous studies have suggested that PAAs are metabolized into genotoxic nitrenium ions. Moreover, ddE, a relative-energy based index derived from quantum chemistry calculations that measures the stability nitrenium ions, has been correlated with mutagenicity.
View Article and Find Full Text PDFBackground: Although the in silico predictive ability of the Ames test results has recently made remarkable progress, there are still some chemical classes for which the predictive ability is not yet sufficient due to a lack of Ames test data. These classes include simple heterocyclic compounds. This study aimed to investigate the mutagenicity and structure-mutagenicity relationships for some heterocycles in the Ames test.
View Article and Find Full Text PDF