Metabolism of 2-acetylaminofluorene. I. Metabolism in vitro, of 2-acetylaminofluorene and 2-acetylaminofluoren-9-one by hepatic enzymes

Abstract

1. 2-Acetylaminofluorene (AAF) was converted by rat liver microsomal and cytosolic enzymes to 2-aminofluorene (AF), 2-glycoloylaminofluorene (GAF), 2-acetylaminofluoren-3-, -7-, and -9-ol (3-, 7-, 9-hydroxy-AAF), and 2-acetylaminofluoren-9-one (AAF-9-one). In addition, a new metabolite MX₁ was detected.

2. AAF was converted by rabbit liver microsomal and cytosolic enzymes to N-hydroxy-AAF, GAF, 5-, 7-, and 9-hydroxy-AAF, AAF-9-one, 5- and 7-hydroxy-AAF-9-one (new compounds), and AF, indicating species differences in the N- and ring-hydroxylation of AAF and secondary oxygenation of AAF. In addition, an unknown metabolite MX₂ was detected.

3. AAF-9-one was converted by rat liver microsomal and cytosolic enzymes to optically active 9-hydroxy-AAF and 7-hydroxy-AAF-9-one; in addition MX₁ was found.

4. Rabbit liver microsomal and cytosolic enzymes converted AAF-9-one to 2-aminofluoren-9-one (AF-9-one), 9-hydroxy-AAF, N-hydroxy-AAF-9-one, GAF-9-one, 7-hydroxy-AAF-9-one, and 7,9-dihydroxy-AAF. In addition, metabolite MX₁ and its dihydro-dihydroxy derivative were found.

5. These results indicate that AAF and AAF-9-one have common metabolic pathways, as AAF after primary oxygenation to 9-hydroxy-AAF and partial dehydrogenation to AAF-9-one, undergoes secondary oxygenation to 7-hydroxy-AAF-one and MX₁ as well as the corresponding dihydro-dihydroxy derivatives.