Apoptosis Modulates Hepatotoxic Effects of 2-Aminoanthracene in Fisher 344 Rat

Document Type


Publication Date



The arylamine 2-amino-anthracene (2-AA) is an aromatic hydrocarbon employed in manufacturing of chemicals, dyes, inks, and as curing agents in epoxy resins and polyurethanes. 2-AA has been detected tobacco smoke and cooked foods. The modulation of the toxic effects of 2-AA on the liver by apoptosis was investigated on twenty four post-weaning 3-4 week old F-344 male rats exposed to 0 mg/kg-diet (control), 50 mg/kg-diet (LD), 75 mg/kg-diet (MD) and 100 mg/kg-diet (HD) 2-AA for 14 [2WK] and 28 days [4WK]. Analysis of total mRNA extracts from liver for apoptosis-related gene expression changes in AEN, BAX, CASP3, JUN, MDM2, P53, and GAPDH genes by qRT-PCR was coupled with liver tissue histology (H&E staining), TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end-labeling) assay and Caspase (Caspase Glo assay) activity. Dose-related histological changes in liver cell architecture were observed at the highest doses in both 2WK and 4WK exposures. Dose-related increases in TUNEL-positive staining were also observed. Caspase3 assays showed dose-dependent increases (2WK) but suppression in LD and MD [4WK] rat livers and an increase in HD rats. Dose-related increases in expression were observed in all genes measured.


Society of Toxicology Annual Meeting (SOT)


Phoenix, AZ