Exploring Transcriptional Relationships Within Fisher-344 Rats Exposed to 2-Aminoanthracene using VisANT Network Modeling and Gene Ontology Tools

摘要

To understand the mechanism of arylamine toxicity, the effect of 2-Aminoanthracene (2-AA) on the pancreas of Fisher-344 rats was investigated. Twenty four post-weaning 3-4 week old F-344 male rats were exposed to 0 mg kg~(-1) diet (control), 50 mg kg~(-1) diet (low dose), 75 mg kg~(-1) diet (medium dose) and 100 mg kg~(-1) diet (high dose) 2-AA for 14 and 28 days. This was followed by analysis of the pancreas for global gene expression changes by Affymetrix Microarray GeneChips. More Gene Ontology (GO) categories were found to be significantly altered for the 14 day study than the 28 day study. In the 14 day study, 45, 57 and 237 cellular component, molecular function and biological process gene ontology categories were found to be significant, respectively. Similarly, 7, 5 and 25 cellular component, molecular function and biological process GO categories were altered, respectively. Some of these GO categories include; modification-dependent protein catabolic process, phospholipid biosynthetic process and glucose. VisANT was employed to analyze the dataset and to explore the biological network relationship between differentially expressed genes. This software was employed to analyze the dataset and to explore the relationships between differentially expressed genes. Three mRNA transcripts were identified from the network plot to have at least 50 links with other genes. These include SLC2A4 (glucose transporting gene), MAPK3 (a signal transduction pathway protein, mitogen activated protein kinase3 and RAD23B (DNA repair protein and ubiquitin-like containing protein). The current study identified altered gene expression profiles associated with pancreatic carcinoma, pancreatitis and/or type 2 diabetes. This may be useful to identify and develop biomarkers as a diagnostic tool associated with the onset of these pathologies.