Hepatic gene expression analysis of 2-aminoanthracene exposed Fisher-344 rats reveal patterns indicative of liver carcinoma and type 2 diabetes.

摘要

The goal of the present study was to examine hepatic differential gene expression patterns in Fisher-344 rats in response to dietary 2-aminoanthracene (2AA) ingestion for 14 and 28 days. Twenty four post-weaning 3-4 week old F-344 male rats were exposed to 0 mgkg(-1)-diet (control), 50 mgkg(-1)-diet (low dose), 75 mgkg(-1)-diet (medium dose) and 100 mgkg(-1)-diet (high dose) 2AA for 14 and 28 days. This was followed by analysis of the liver for global gene expression changes. In both time points, the numbers of genes affected seem to correlate with the dose of 2AA. Sixteen mRNAs were differentially expressed in all treatment groups for the short-term exposure group. Similarly, 51 genes were commonly expressed in all 28-day exposure group. Almost all the genes seem to have higher expression relative to the controls. In contrast, cytochrome P450 family 4, subfamily a, polypeptide 8 (Cyp4a8), and monocyte to macrophage differentiation-associated (Mmd2) were down-regulated relative to controls. Differentially expressed mRNAs were further analyzed for associations via DAVID. GO categories show the effect of 2AA to be linked with genes responsible for carbohydrate utilization and transport, lipid metabolic processes, stress responses such as inflammation and apoptosis processes, immune system response, DNA damage response, cancer processes and circadian rhythm. The data from the current study identified altered hepatic gene expression profiles that may be associated with carcinoma, autoimmune response, and/or type 2 diabetes. Possible biomarkers due to 2AA toxicity in the liver for future study include Abcb1a, Nhej1, Adam8, Cdkn1a, Mgmt, and Nrcam.