N-Acetyltransferase 1 Polymorphism and Breast Cancer Risk

Abstract

Human arylamine N-acetyltransferases 1 (NAT1) is a phase II cytosolic enzyme responsible for the biotransformation of many arylamine compounds including pharmaceuticals and environmental carcinogens. A common environmental carcinogen found in cigarette smoke is an aromatic amine, 4-aminobiphenyl (ABP). Arylamines such as ABP can either be inactivated via N-acetylation or activated via O-acetylation by NAT1. ABP can be N-acetylated and then excreted from the body. However, if ABP is first hydroxylated by cytochrome p450 1A1 (CYP1A1), the hydroxyl-ABP then can be further activated by NAT1-catalyzed O-acetylation resulting in N-acetoxy-ABP. This compound is very unstable and spontaneously degrades to form a nitrenium ion that can react with DNA to produce bulky adducts. If these adducts are not repaired, mutagenesis can occur and result in cancer initiation.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2010
Accession Number
ADA543991

Entities

People

  • Lori Millner

Organizations

  • University of Louisville

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Acetylation
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Carcinogens
  • Cell Physiological Processes
  • Electrospray Ionization
  • Formic Acid
  • Genes
  • Genetic Variation
  • Genetics
  • Liquid Chromatography
  • Mass Spectrometers
  • Mass Spectrometry
  • Neoplasms
  • Spectrometry

Fields of Study

  • Chemistry

Readers

  • Allergy and Immunology.
  • Analytical Chemistry
  • Molecular Genetics