Global Pancreatic Gene Expression Analysis of Fisher-344 Male Rats Indicates SLC2A4 (Glucose Transporter) Gene to Play Important Role in the Toxicity Effects of 2-Aminoanthracene Exposure

The effect of 2-aminoanthracene (2-AA) on the islets of Langerhans was investi-gated by exposing twenty four post-weaning 3-4 week old F-344 male rats to 0 mg/kg (control), 50 mg/kg (low dose), 75 mg/kg (medium dose) and 100 mg/kg (high dose) 2-AA for 14 and 28 days followed by analysis of the pancreas for broad gene expression changes by Affymetrix Microarray GeneChips. Arylamine 2-AA is an aromatic hydrocarbon employed in the manufacturing of agricultural chemicals, drugs, dyes, road tars, synthetic fuels, inks, plastics as rubber antioxidants, curing agents in the synthesis of epoxy resins and of polyurethanes. Other sources of expo-sure of this chemical include tobacco smoking and cooked foods. Results showed more gene ontology (GO) categories were found to be significant for the two week study than the four week study. With respect to the 14 day study, 45, 57 and 237 cellular component, molecular function and biological process gene ontology cate-gories were found to be significant respectively. Similarly, a respective 7, 5 and 25 cellular component, molecular function and biological process. Some of these GO categories include; modification-dependent protein catabolic process, phospholipid biosynthetic process, glucose metabolic process, small ribosomal subunit, ubiquitin ligase complex, proteasome complex and Golgi apparatus, ligase activity, cofactor binding and sequence-specific DNA binding. To explore the relationships between differentially expressed genes, VisANT, interactive software platform that enables biological network modeling was employed to analyze the dataset. 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 trans-duction pathway protein, mitogen activated protein kinase 3 and RAD23B (DNA repair protein and ubiquitin-like containing protein).