Back to Search
Start Over
Novel miRNA biomarkers for genotoxicity screening in mouse.
- Source :
-
Toxicology [Toxicology] 2018 Jul 01; Vol. 404-405, pp. 68-75. Date of Electronic Publication: 2018 May 16. - Publication Year :
- 2018
-
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.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1879-3185
- Volume :
- 404-405
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 29777724
- Full Text :
- https://doi.org/10.1016/j.tox.2018.05.009