N- and O-deacetylation of N-acetoxy-N-arylacetamides by mammalian hepatic microsomes.

The present study demonstrates that hepatic microsomes from guinea pigs, rats, mice, hamsters, rabbits and dogs catalyze N-deacetylation of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxy-3,2'-dimethyl-4-acetylaminobiphenyl and O-deacetylation of N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) and N-acetoxy-3,2'-dimethyl-4-acetylaminobiphenyl (N-AcO-DMAABP). Gel filtration resolves the solubilized guinea pig microsomal enzymes into two deacetylases. The larger molecular weight enzyme catalyzes N-deacetylation of N-OH-AAF, whereas the smaller one cannot. Both enzymes catalyze O-deacetylation of N-AcO-AAF and N-AcO-DMAABP, but the activity is mainly due to the larger enzyme. Guinea pig and rat liver microsomes also catalyze N-deacetylation of N-AcO-AAF resulting in the binding of 2-aminofluorene to nucleic acids, but the activities are much less than that of the O-deacetylation of N-AcO-AAF. Thus, the amino-fluorene-DNA adducts which have been found in intact cells treated with N-AcO-AAF may result directly from N-deacetylation or indirectly from N,O-acetyltransfer following O-deacetylation.