Metabolic activation of 3-aminodibenzofuran mediated by P450 enzymes and sulfotransferases.

ABSTRACT

3-Aminodibenzofuran (3-ADBF) is a potent bladder carcinogen. This study aimed to identify reactive metabolites and the metabolic pathways of 3-ADBF. The in vitro and in vivo studies demonstrated that 3-ADBF was oxidized to the corresponding hydroxylamine by cytochrome P450 enzymes, followed by sulfation of the hydroxyl group mediated by sulfotransferases. The resulting sulfate conjugate was chemically reactive to GSH and cysteine residues of hepatic protein to form the corresponding GSH conjugate and protein adduction. Exposure of 3-ADBF to primary hepatocytes caused protein covalent binding and decreased cell viability. The resultant protein adduction was found to correlate the observed cytotoxicity of 3-ADBF.