Apoptosis Modulates Hepatotoxic Effects of 2-Aminoanthracene in Fisher 344 Rat
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)
Gato, Worlanyo E., Dale B. Hales, Stacey R. McGee, Jay C. Means.
"Apoptosis Modulates Hepatotoxic Effects of 2-Aminoanthracene in Fisher 344 Rat."
Chemistry Faculty Presentations.