Publications by authors named "Katsutoshi Ohno"

Efforts have been made to replace animal experiments in safety evaluations, including in vitro-based predictions of human internal exposures, such as predicting peak plasma concentration (Cmax) values for xenobiotics and comparing these values with in vitro-based toxicity endpoints. Herein, the authors predicted the Cmax values of food-related compounds in humans based on existing and novel in vitro techniques. In this study, 20 food-related compounds, which have been previously reported in human pharmacokinetic or toxicokinetic studies, were evaluated.

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Article Synopsis
  • The study focuses on creating an in vitro method to evaluate how compounds are excreted through bile in humans, which is crucial for understanding drug behavior and toxicity.
  • Researchers successfully developed a culture system using human liver cells (hepatocytes) that forms functional bile canaliculi, confirming its ability to assess compound uptake and biliary excretion over 21 days.
  • The findings indicated that certain pharmaceutical and food-related compounds showed positive biliary excretion indices, suggesting that this new system could be a reliable tool for predicting drug excretion patterns.
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Pharmacokinetic prediction after oral ingestion is important for quantitative risk assessment of food-derived compounds. To evaluate the utility of human intestinal absorption prediction, we compared the membrane permeability and metabolic activities of human induced pluripotent stem cell-derived small intestinal epithelial cells (hiPSC-SIECs) with Caco-2 cells or human primary enterocytes (hPECs). We found that membrane permeability in hiPSC-SIECs had better predictivity than that in Caco-2 cells against 21 drugs with known human intestinal availability (r = 0.

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Tree nuts comprise a category of food allergens that must be included in the food labels in several countries. We developed a polymerase chain reaction (PCR) method using eight specific primer pairs to detect eight representative tree nuts (almond, Brazil nut, cashew, hazelnut, macadamia nut, pecan, pistachio, and walnut) under the same experimental conditions. The specificity of the eight primer pairs was confirmed by PCR testing against a variety of plant and animal samples.

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Genotoxicity assessment is important for predicting the carcinogenicity of chemical substances. p53R2 is a p53-regulated gene that is induced by various genotoxic stresses. We previously developed a p53R2-dependent luciferase reporter gene assay in the MCF-7 human breast adenocarcinoma cell line, and demonstrated its ability to detect genotoxic agents.

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Tumor promoters can cause development of tumors in initiated cells and the majority of them are non-genotoxic carcinogens. The detection of tumor promoters is important for the prevention of cancer. The in vitro two-stage transformation assay, using BALB/c 3T3 cells, is a useful system, and benefits from a convenient protocol and high predictability of mammalian carcinogenicity.

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The tumor suppressor, p53, plays an important role in DNA damage repair, by regulating the expression of target genes. One p53-target gene, p53R2, which encodes a subunit of ribonucleotide reductase, is activated by DNA damage. We have previously developed a genotoxicity test system, using human cell lines and a p53R2-dependent luciferase reporter gene assay.

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The oxidation of oils has important effects on the quality of oily foods, such as instant noodles. In particular, the generation of aldehydes, which accompanies the oxidation of oils, is one of the first factors to reduce food quality. We examined various indicators of oil quality during temperature-accelerated storage and found that peroxide value (POV) was highly correlated with the total concentration of major odorants.

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p53R2, which encodes a subunit of ribonucleotide reductase, is activated by DNA damage induced by gamma-ray and ultraviolet irradiation, and also by genotoxic chemicals such as adriamycin. For the purpose of constructing an easy-operating genotoxicity test system using human cell lines, we developed a p53R2-dependent luciferase reporter gene assay, and demonstrated dose-dependent luminescence caused by adriamycin in two human cell lines that express wild-type p53, MCF-7 and HepG2. The performance of this assay system was evaluated with 80 chemicals including those known in the Ames test as genotoxic or non-genotoxic.

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Leptothrix cholodnii is an aerobic sheath-forming bacterium often found in oligotrophic and metal-rich aquatic environments. The sheath of this bacterium was isolated by selectively lysing the cells. Glycine and cysteine were the major amino acids of the sheath.

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A PCR assay for the detection of Bacillus cereus strains able to produce an emetic toxin (cereulide) was developed in this study based on a sequence-characterized amplified region (SCAR) derived from a random amplified polymorphic DNA (RAPD) fragment. One of the RAPD fragments generated was selected, cloned, and sequenced. A set of PCR primers was newly designed from the SCAR obtained (the sequence of the cloned RAPD fragment) and used in this assay.

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