Identification of Peptides from Liver Tissues of 2-Aminoanthracene Exposed Fisher-344 Rats

The toxicity associated with 2-aminoanthracene (2-AA) exposure in Fisher-344 (F-344) rats was investigated using proteomics approach. Twenty four post-weaning 3-4 week old F-344 male rats were fed diets of 0 mg/kg-diet (control), 50 mg/kg-diet (low dose), 75 mg/kg-diet (medium dose) and 100 mg/kg-diet (high dose) 2-AA for 14 and 28 days. This was followed by total protein extraction from liver tissues. Protein samples were separated using one dimensional gel electrophoresis. The gel digests were analyzed by nano LC/MS/MS with a Waters NanoAcquity HPLC system. Generated data were searched using Mascot and quantified via spectral counting. There seem to be more proteins expressed in the short-term study than the long term study. Using a variety of artifactual examination, oxidation and deamidation modifications were greater than acetyl and pyro-Glu protein modifications in both treatment groups. Although the 14 day exposure group showed, greater level of proteins expressed than the 28 day treatment animals, these were not analyzed from the similar size bands. Hemopexin, Adenosylhomocysteinase, Calreticulin, Gc vitamin D-binding protein and Fetub protein may be important in mediating the toxicity of 2-AA. Using relationships analytical tool, SLC2A4 and MAPK3 were found to interact with several proteins identified from the current study. The nature of this interaction is unknown at this point. Understanding the role of SLC2A4 in regulating other proteins as observed in the study will be pursued in future investigations. Combining the current data with other toxicogenomic data from the liver and pancreas will be useful in developing biomarkers due to arylamine toxicity.