Bioactivation of the human carcinogen aristolochic acid

Abstract

quinone oxidoreductase, the ability of aristolochic acid I to bind DNA covalently was increased significantly by addition of PAPS and SULT1B1. We conclude from these studies that AL-NOHs, formed following partial nitroreduction of aristolochic acids, serve as substrates for SULT1B1, producing N-sulfated esters, which, in turn, are converted to highly active species that react with DNA and, potentially, cellular proteins, resulting in the genotoxicity and nephrotoxicity associated with ingestion of aristolochic acids by humans.