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.

Details

• Personal Author:
  Corbett BR ; Corbett MD ; Johnston JJ ; Lim LO ; Wiebkin P
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Amino Acids Chemistry Laboratories Neoplasms Nitrogen Compounds Occupational Health Safety
• Keywords:
  Amino-compounds Bioactivation Biotransformation Cancer Chemical-structure In-vitro-studies Laboratory-animals Liver-cells NIOSH-Grant NIOSH-Publication Nucleic-acids Organo-nitrogen-compounds

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• ISSN:
  0893-228X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Florida ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  41-46
• Volume:
  1
• Issue:
  1
• NIOSHTIC Number:
  nn:00177783
• Citation:
  Chem Res Toxicol 1988 Jan; 1(1):41-46
• Contact Point Address:
  Michael D. Corbett, Building 120, University of Florida, Gainesville, FL 32611
• CAS Registry Number:
  N-Hydroxy-2-(acetylamino)fluorene (CAS RN 53-95-2)
• Federal Fiscal Year:
  1988
• Performing Organization:
  University of Florida, Gainesville, Florida
• Peer Reviewed:
  True
• Start Date:
  19840801
• Source Full Name:
  Chemical Research in Toxicology
• End Date:
  19870731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ce0bc2dc01adfa9e3c68694e76d1aa33fc41bc715037dbbf033d0d1778b4b7dd67297f20dbccafd58e9c17d9ce52b1a5813dc09a19f75109a76f42e43940ba67
• Download URL:
  https://stacks.cdc.gov/view/cdc/185463/cdc_185463_DS1.pdf
• File Type:
  [PDF - 802.89 KB ]