Accelerated Cytotoxicity Mechanism Screening of 4-Aminobiphenyl in an in vitro Hepatocyte Inflammation Model

• Main Author: Delaney, Sarah
• Other Authors: O'Brien, Peter J.
• Language: en_ca
• Published: 2011
• Subjects: Cytotoxicity; Aromatic Amine; 0491
• Online Access: http://hdl.handle.net/1807/29521

4-Aminobiphenyl is an aromatic amine compound that is present in cigarette smoke, diesel exhaust, cooking oil fumes and dye intermediates. It is a well-known human bladder carcinogen and liver carcinogen in experimental animals that is metabolically activated by liver CYP1A1/2. We have used the “Accelerated Cytotoxicity Mechanism Screening” (ACMS) techniques to analyze the molecular cytotoxic mechanisms of 4-aminobiphenyl. Hepatocyte exposure to an inflammatory system significantly increased hepatocyte susceptibility to 4-aminobiphenyl. 4-Aminobiphenyl- induced cytotoxicity and lipid peroxidation were both prevented by altering cellular redox status and with the addition of antioxidants. Toxicity was increased with the depletion of hepatocyte GSH levels and by inhibiting N-acetyltransferase. These results will provide more insight into the cytotoxic and genotoxic mechanisms of 4-aminobiphenyl and also suggest that inflammation may be responsible for an increase in arylamine carcinogenesis.