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The anti-tumour activity of the novel thiazolidinedione class peroxisome proliferator-activated receptor gamma (PPARgamma) agonist CS-7017 was investigated. CS-7017 activated PPARgamma-mediated luciferase expression with an EC(50) of 0.20 nM. In addition, CS-7017 was shown to be highly selective for PPARgamma amongst other PPAR subfamilies. CS-7017(More)
The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of(More)
Conducting the single-cell gel electrophoresis (Comet) assay in the urinary bladders of rodents is technically problematic because the bladder is small and thin, which makes it difficult to collect its mucosal cells by scraping. We performed the Comet assay using a simple mincing method in which tissues are minced with scissors. We then compared data(More)
The in vivo comet assay has been used for the evaluation of DNA damage and repair in various tissues of rodents. However, it can give false-positive results due to non-specific DNA damage associated with cell death. In this study, we examined whether the in vivo comet assay can distinguish between genotoxic and non-genotoxic DNA damage in urinary bladder(More)
The reproducibility of the in vivo Pig-a gene mutation test system was assessed across 13 different Japanese laboratories. In each laboratory rats were exposed to the same dosing regimen of N-nitroso-N-ethylurea (ENU), and red blood cells (RBCs) and reticulocytes (RETs) were collected for mutant phenotypic analysis using flow cytometry. Mutant frequency(More)
As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM) international validation study of in vivo rat alkaline comet assays, we examined cadmium chloride, chloroform, and D,L-menthol under blind conditions as coded chemicals in the liver and stomach of Sprague-Dawley rats after 3 days of administration. Cadmium chloride showed(More)
2-Nitroanisole (2-NA) is used in the manufacturing of azo dyes and causes cancer, mainly in the urinary bladder. Previous in vivo genotoxic data seems to be insufficient to explain the mechanism through which 2-NA induces carcinogenesis, and several bladder carcinogens were reported to induce oxidative DNA damage. Thus, we examined the potential induction(More)
The in vivo mutation assay using the X-linked phosphatidylinositol glycan class A gene (Pig-a in rodents, PIG-A in humans) is a promising tool for evaluating the mutagenicity of chemicals. Approaches for measuring Pig-a mutant cells have focused on peripheral red blood cells (RBCs) and reticulocytes (RETs) from rodents. The recently developed PIGRET assay(More)
The PIGRET assay, which was developed as the Pig-a assay in reticulocytes, can detect mutagenicity of compounds earlier than the Pig-a assay in total red blood cells (RBC; RBC Pig-a assay). The usefulness of the PIGRET assay as a short-term test has been confirmed in a collaborative study in Japan with 24 chemicals. One of these chemicals,(More)
Exposure to environmental agents can compromise numerous immunological functions. Immunotoxicology focuses on the evaluation of the potential adverse effects of xenobiotics on immune mechanisms that can lead to harmful changes in host responses such as: increased susceptibility to infectious diseases and tumorigenesis; the induction of hypersensitivity(More)