Metabolism of acridine by rat-liver enzymes

Metabolism of acridine by S10 fractions from control adult male Sprague-Dawley rats produces mainly 9- acridone , apparently catalyzed by aldehyde oxidase ( ED1 .2.3.1). In contrast, the predominant metabolic product produced by the corresponding S10 fraction of PCB-induced liver enzymes is a dihydrodiol (either the 2,3- or 3,4-isomer) presumably derived from an epoxide. Several minor metabolites of unknown structure are also formed. During in vitro reactions aldehyde oxidase requires neither atmospheric oxygen nor NADPH. Acridine has been reported to be mutagenic to Salmonella typhimurium, but only in the absence of PCB-induced activating enzymes. It also has been reported to produce chromosomal aberrations in cultured Chinese hamster cells both with and without enzymatic activation. While a connection between aldehyde oxidase catalysis and mutagenic action of acridine has not been established, the extensive metabolic potential of this compound implies that complete description of mutagenicity will be difficult.