Abstract：
:Two 2-aminofluorene-derived hydroxamic acids that differ only in the nature of the N-acyl group were examined for their relative abilities to undergo covalent binding to nucleic acids. Studies of the bioactivation of N-hydroxy-N-acetyl-2-aminofluorene (N-OH-AAF) and N-hydroxy-N-glycolyl-2-aminofluorene (N-OH-GAF) were conducted with hepatocyte suspensions and subcellular fractions prepared from male Sprague-Dawley rats. Both hydroxamic acid substrates displayed equal binding to both DNA and RNA after incubations with hepatocyte suspensions. The extent of binding of each substrate was approximately the same for DNA and RNA. Investigations with subcellular fractions revealed some major differences between the probable mechanisms by which the two substrates were covalently bound to exogenous DNA. In agreement with the prior literature reports, N-OH-AAF was extensively bound to DNA through the action of cytosol enzymes, including both N,O-acyltransferase and sulfotransferase. The microsomal enzyme fraction also catalyzed binding to DNA, and this process was completely inhibited by paraoxon. The covalent binding of N-OH-GAF to DNA was catalyzed by cytosol enzymes to a significant extent only in the presence of 3'-phosphoadenosine-5'-phosphosulfate, which suggests the action of sulfotransferase. Covalent binding of N-OH-GAF to DNA was minimal through the action of cytosolic N,O-acyltransferase, which confirms our earlier observation that N-OH-GAF is a potent suicide inhibitor of this enzyme. The microsomal fraction catalyzed the binding of N-OH-GAF to DNA at a rate that was about twice that observed for N-OH-AAF.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Corbett MD,Lim LO,Corbett BR,Johnston JJ,Wiebkin Pdoi
10.1021/tx00001a008subject
Has Abstractpub_date
1988-01-01 00:00:00pages
41-6issue
1eissn
0893-228Xissn
1520-5010journal_volume
1pub_type
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