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Diethylnitrosamine- and partial hepatectomy-induced decrease in alpha 2u-globulin mRNA level in the rat liver
1Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Japan.
Abstract:
Changes in gene expression in the rat liver were investigated by analyzing cDNA libraries for liver mRNAs from adult male rats injected with a chemical carcinogen diethylnitrosamine (DEN). Differential screening using normal and DEN-treated liver cDNAs as probes demonstrated that some of the mRNA species had noticeably lower abundance in the DEN-treated liver than in the untreated liver. Surprisingly, most of those clones were found to code for alpha 2u-globulin (A2uG), an abundant protein in the male rat liver. Further analysis by in situ hybridization revealed that the decrease in the A2uG mRNA level occurred in the area where liver cells were proliferating due to DEN treatment and/or partial hepatectomy (PH). The findings indicate coincidence of cell proliferation with a decrease in the A2uG gene expression in the adult male rat liver, implying that the A2uG-related change favors chemical carcinogen-induced cell growth.
Insights
Diethylnitrosamine (DEN) carcinogen exposure in male rats led to decreased alpha 2u-globulin (A2uG) gene expression. This reduction coincided with liver cell proliferation, suggesting A2uG changes may support carcinogen-induced liver growth.
Area of Science:
- Hepatology
- Molecular Biology
- Toxicology
Background:
- Alpha 2u-globulin (A2uG) is an abundant protein in adult male rat liver.
- Chemical carcinogens can induce significant changes in liver gene expression.
Purpose of the Study:
- To investigate alterations in rat liver gene expression following exposure to the chemical carcinogen diethylnitrosamine (DEN).
- To determine the relationship between DEN-induced liver cell proliferation and specific gene expression changes.
Main Methods:
- Analysis of cDNA libraries from normal and DEN-treated adult male rat livers.
- Differential screening of mRNA species.
- In situ hybridization to localize A2uG mRNA levels.
Main Results:
- DEN treatment resulted in a decreased abundance of certain mRNA species in the liver.
- Most downregulated mRNAs were identified as coding for alpha 2u-globulin (A2uG).
- Reduced A2uG mRNA levels were observed in areas of DEN-induced liver cell proliferation.
Conclusions:
- A decrease in alpha 2u-globulin (A2uG) gene expression is associated with liver cell proliferation in adult male rats treated with DEN.
- These findings suggest that changes in A2uG expression may play a role in promoting chemical carcinogen-induced liver cell growth.