Pancreatic Gene Expression Altered Following Dietary Exposure to 2-Aminoanthracene: Links to Diabetogenic Activity

The mutagen 2-aminoanthracene (2-AA) is an aromatic amine or arylamine, which belongs to a class of polycyclic aromatic hydrocarbons. 2-AA is used in the manufacturing of a wide variety of chemicals, drugs, dyes and polymers. Non-occupational sources include tobacco smoking and cooked foods. The goal of this study is to evaluate pancreatic gene expression patterns in Fischer-344 (F-344) male rats exposed to 2-AA. As a first step the effects of 2-aminoanthracene exposure on the pancreas with particular interest in genes that relate to insulin and insulin metabolism. To achieve this goal, 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 followed by analysis of the pancreas for broad gene expression changes. Results obtained from our study suggest most of the mRNA transcripts that were differentially expressed are involved in energy metabolism in the pancreas, protein digestion and some that play an active role in pancreatitis and pancreatic cancer. Some of these genes include: insulin, colipase pancreatic, carboxypeptidase, chymotrypsinogen B1 and chymotrypsin C (caldecrin). These findings seem to point to the role of 2-AA in the dysregulation of several pancreatic genes that regulate lipid and protein metabolism in a way that involves a feedback mechanism which may ultimately lead to insulin resistance and tissue autolysis. Quantitative PCR determination of fold changes in selected genes show similar trends to global expression determined via microarray analyses.