1. Novel miRNA biomarkers for genotoxicity screening in mouse.
- Author
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Oka H, Masuno K, Uehara T, Okamoto T, Matsuura Y, Nakano T, and Yamaguchi S
- Subjects
- Animals, Biomarkers blood, Biomarkers metabolism, Comet Assay methods, DNA Damage physiology, Diethylhexyl Phthalate toxicity, Liver drug effects, Male, Mice, Mice, Inbred ICR, Plasticizers toxicity, DNA Damage drug effects, Liver metabolism, MicroRNAs blood, Mutagenicity Tests methods
- Abstract
The genotoxic potential of drugs is a serious problem, and its evaluation is one of the most critical processes of drug development. Although the comet assay of compound-exposed tissue is a frequently used genotoxicity test, its high false-positive rate is a major complication, and we consistently obtained false-positive results using the comet assay of mouse liver for nine hepatotoxic non-genotoxins (NGTXs). To identify novel genotoxin (GTX)-specific biomarkers, we screened the expression of 750 microRNAs (miRNAs) in the livers of mice treated with GTXs or NGTXs. Three miRNAs, miR-22-3p, miR-409-3p, and miR-543-3p, were significantly down-regulated in GTX-treated mouse liver. In contrast, these three miRNAs were significantly up-regulated in plasma. A discrimination model based on the expression levels of these biomarkers successfully identified GTXs and NGTXs. This novel biomarker expression-based discrimination model analysis using both liver and plasma is effective for detecting genotoxicity with high sensitivity and reliability to support drug development., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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