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c-myc gene amplification during hepatocarcinogenesis by a choline-devoid diet
N Chandar1, B Lombardi, J Locker
1Department of Pathology, University of Pittsburgh, PA 15261.
Summary
A choline-devoid diet induces liver tumors in rats by amplifying the c-myc gene. This gene amplification, linked to increased expression, may be a critical early step in liver cancer development.
Area of Science:
- Hepatology
- Molecular Biology
- Carcinogenesis
Background:
- Liver tumors can develop in rats consuming a choline-devoid diet without carcinogens.
- The c-myc gene is frequently implicated in various cancers.
Purpose of the Study:
- To investigate the role of c-myc gene amplification in rat liver tumors induced by a choline-devoid diet.
- To explore the relationship between c-myc gene amplification, expression, and diet.
Main Methods:
- Rats were fed a choline-devoid diet, with some subsequently receiving a choline-supplemented diet.
- Tumor tissues and surrounding liver regions were analyzed for c-myc gene amplification and expression levels.
Main Results:
- All analyzed liver tumors (13/13) exhibited c-myc gene amplification, ranging from 2- to 70-fold.
- Increased c-myc gene expression accompanied the amplification.
- Higher c-myc amplification was observed in tumors from rats switched to a choline-supplemented diet; low-level amplification was also found in non-tumorous liver regions of these rats.
Conclusions:
- A choline-devoid diet serves as an effective in vivo model for inducing gene amplification in rat liver.
- c-myc gene amplification is a consistent and potentially early event in choline-deficiency-induced rat liver carcinogenesis.