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Updated: Aug 9, 2026
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Gene expression analysis in mice liver on hepatocarcinogenesis by flumequine
Yoko Kashida1, Akiko Takahashi, Mitsuyoshi Moto
1Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 183-8509 Fuchu, Tokyo, Japan. kashida.1@osu.edu
Abstract:
mRNA expression profiles in the liver from mice treated with flumequine (FL) were analyzed in order to elucidate the mechanism of its tumor-promoting effect. The liver from a C3H/He mouse that received a diet containing 4,000 ppm of FL for 4 weeks was examined by cDNA microarray in comparison with an untreated mouse. Furthermore, to obtain a more comprehensive sequence, time-course changes in selected genes were determined by real-time RT-PCR. Microarray analysis revealed 15 upregulated and 9 downregulated genes in an FL-treated mouse. The upregulated genes included signal transducers and cell cycle regulators. In addition, the levels of stress response genes, particularly glutathione S-transferase (GST) alpha and GSTmu, were very high, indicating the generation of oxidative stress. On the other hand, the downregulated genes included phase I metabolic enzymes, such as cytochrome P450 (CYPs) enzymes, and apoptosis-associated proteins. These changes were confirmed by quantitative RT-PCR and were generally consistent with each other. Time-course observations revealed consistent results, particularly with regard to GSTalpha, GSTmu, ERK5, and CYP2E1. In addition, the expression of 8-oxoguanine DNA glycosylase 1 (OGG1) was increased in a time-dependent manner. These results suggest the possibility that responses against oxidative stress may play a major role in hepatocarcinogenesis by FL in mice.
Insights
Flumequine (FL) exposure in mice liver increases stress response genes like glutathione S-transferase (GST) and oxidative stress markers. This suggests oxidative stress responses may drive flumequine-induced liver cancer.
Area of Science:
- Hepatocarcinogenesis
- Molecular Biology
- Toxicology
Background:
- Flumequine (FL) is an antibiotic with suspected tumor-promoting effects.
- Understanding the molecular mechanisms behind FL's carcinogenicity is crucial for risk assessment.
Purpose of the Study:
- To investigate the mRNA expression profile in mouse liver following flumequine treatment.
- To elucidate the mechanism of flumequine's tumor-promoting effect by analyzing gene expression changes.
Main Methods:
- cDNA microarray analysis was performed on liver tissue from flumequine-treated and untreated mice.
- Quantitative real-time RT-PCR was used to confirm microarray findings and analyze time-course gene expression changes.
Main Results:
- Flumequine upregulated 15 genes, including signal transducers and cell cycle regulators.
- Flumequine significantly increased stress response genes like glutathione S-transferase (GST) alpha and GSTmu, indicating oxidative stress.
- Flumequine downregulated phase I metabolic enzymes (e.g., cytochrome P450s) and apoptosis-associated proteins.
- Time-course analysis confirmed increased expression of GSTalpha, GSTmu, ERK5, CYP2E1, and 8-oxoguanine DNA glycosylase 1 (OGG1).
Conclusions:
- Flumequine treatment induces oxidative stress in mouse liver.
- The observed gene expression changes, particularly those related to oxidative stress, suggest a potential role in flumequine-induced hepatocarcinogenesis.
