© 1988 Oxford University Press
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N- and O-deacetylation of N-acetoxy-N-arylacetamides by mammalian hepatic microsomes
1Department of Chemical Carcinogenesis, Michigan Cancer Foundation 110 E. Warren, Detroit, MI 48201, USA
2Present address: Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan
3To whom correspondencd should be addressed
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-acetylamino-biphenyl(N-AcO-DMAABP). Gel filtration resolves el filtration resolves the solu-bilizedolu-bilized 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-deacety-lation of N-AcO-AAF resulting in the binding of 2-amino-fluorene 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-deacety-lation or indirectly from N,O-acetyltransfer following O-deacetylation.