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

Journal Article · Fri Jan 01 04:00:00 EST 1988 · Chem. Res. Toxicol.; (United States)

DOI:https://doi.org/10.1021/tx00001a008· OSTI ID:5900382

Corbett, M D; Lim, L O; Corbett, B R; Johnston, J J; Wiebkin, P

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 inhibition 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. 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. As in the case of N-OH-AAF binding, this microsomal-catalyzed binding of N-OH-GAF was prevented by paraoxon. It was proposed that the nucleic acid adducts from N-OH-GAF should possess a much higher percent of adducts which retain the acyl group relative to those adducts resulting from N-OH-AAF bioactivation.

• Research Organization: Univ. of Florida, Gainesville (USA)
• OSTI ID: 5900382
• Journal Information: Chem. Res. Toxicol.; (United States), Journal Name: Chem. Res. Toxicol.; (United States) Vol. 1:1; ISSN CRTOE
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMAL CELLS
ANIMALS
AROMATICS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
CELL CONSTITUENTS
COMPARATIVE EVALUATIONS
CONDENSED AROMATICS
COVALENCE
DNA
DNA ADDUCTS
ENZYME ACTIVITY
ENZYMES
FLUORENE
HYDROCARBONS
KINETICS
LIVER CELLS
MAMMALS
METABOLISM
MICROSOMES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
RATS
REACTION KINETICS
RNA
RODENTS
SOMATIC CELLS
SYNTHESIS
TRANSFERASES
VERTEBRATES