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Covalent binding of N-hydroxy-N-acetyl-2-aminofluorene and N-hydroxy-N-glycolyl-2-aminofluorene to rat hepatocyte DNA: in vitro and cell-suspension studies.

Authors
Corbett-MD; Lim-LO; Corbett-BR; Johnston-JJ; Wiebkin-P
Source
Chem Res Toxicol 1988 Jan; 1(1):41-46
NIOSHTIC No.
00177783
Abstract
The covalent binding of N-hydroxy-N-acetyl-2-aminofluorene (53952) (NOHAAF) and N-hydroxy-N-glycolyl-2-aminofluorene (NOHGAF) to rat hepatocyte DNAwas studied in-vitro. Hepatocyte suspensions prepared from male Sprague-Dawley-rats were incubated with carbon-14 labeled NOHAAF or NOHGAF for 2 hours. The extent of binding of NOHAAF and NOHGAF to cellular DNA and RNA was determined. Both NOHAAF and NOHGAF were bound to DNA and RNA to about the same extent. Cytosolic and microsomal fractions were prepared from livers of Sprague-Dawley-rats. These were incubated with NOHAAF or NOHGAF in the presence or absence of 3'-phospho-adenosine-5'-phosphosulfate (PAPS). The rate and extent of metabolism were determined. Calf thymus DNA was incubated with NOHAAF or NOHGAF in the presence or absence of rat liver cytosol, microsomes or PAPS and the extent of NOHAAF or NOHGAF DNA binding was determined. In some experiments metabolized by rat liver cytosol. NOHAAF was metabolized at a much faster rate and to a greater extent than NOHGAF; however, this difference was largely eliminated when PAPS was present. The microsomal fraction also metabolized both substrates, NOHGAF being metabolized at a much faster rate. Binding of NOHAAF to calf thymus DNA was catalyzed by rat liver cytosol. NOHGAF binding to calf thymus DNA was also catalyzed by rat liver cytosol but only in the presence of PAPS. The microsomal preparation catalyzed binding of NOHAAF and NOHGAF to calf thymus DNA. Paraoxon inhibited NOHAAF and NOHGAF DNA binding in all cases. The authors suggest that nucleic acid adducts of NOHGAF retain a larger proportion of their acyl groups than those of NOHAAF.
Keywords
NIOSH-Publication; NIOSH-Grant; Cancer; Organo-nitrogen-compounds; Amino-compounds; In-vitro-studies; Liver-cells; Laboratory-animals; Nucleic-acids; Biotransformation; Chemical-structure; Bioactivation
Contact
Food Science & Human Nutrition Univeristy of Florida Gainesvile, FL 32611 Gainesville, Florida 32611
CODEN
CRTOEC
CAS No.
53-95-2
Publication Date
19880101
Document Type
Journal Article
Funding Amount
201902.00
Funding Type
Grant
Fiscal Year
1988
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-02027
Issue of Publication
1
Source Name
Chemical Research in Toxicology
State
FL
Performing Organization
University of Florida, Gainesville, Florida
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