Novel miRNA biomarkers for genotoxicity screening in mouse

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 o...

Full description

Saved in:
Bibliographic Details
Published in:Toxicology (Amsterdam) 2018-07, Vol.404-405, p.68-75
Main Authors: Oka, Hiroyuki, Masuno, Koichi, Uehara, Takeki, Okamoto, Toru, Matsuura, Yoshiharu, Nakano, Toru, Yamaguchi, Shinpei
Format: Article
Language:English
Subjects:
Animals
Biomarkers - blood
Biomarkers - metabolism
Comet assay
Comet Assay - methods
Diethylhexyl Phthalate - toxicity
DNA Damage - drug effects
DNA Damage - physiology
Genotoxicity
Liver - drug effects
Liver - metabolism
Male
Mice
Mice, Inbred ICR
MicroRNA
MicroRNAs - blood
Mouse
Mutagenicity Tests - methods
Plasticizers - toxicity
Toxicogenomics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0300-483X
1879-3185
DOI:10.1016/j.tox.2018.05.009