2-Aminofluorene-DNA adduct levels in tumor-target and nontarget organs of rapid and slow acetylator Syrian hamsters congenic at the NAT2 locus

Toxicol Appl Pharmacol. 1996 Nov;141(1):248-55. doi: 10.1006/taap.1996.0281.

Abstract

DNA adduct formation is an important initial event in chemical carcinogenesis. Metabolic activation and deactivation pathways are involved in aromatic amine carcinogenesis, and genetic polymorphism in the N-acetyltransferase 2 (NAT2) gene is associated with differential susceptibility to cancer from aromatic amine chemicals. In the present study, aromatic amine-DNA adduct levels were measured in rapid (Bio. 82.73/H-Patr) and slow (Bio. 82.73/H-Patr) acetylator Syrian hamsters congenic at the NAT2 locus following a single injection of 2-aminofluorene (60 mg/kg). The major DNA adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene (C8-AF), was detected and quantitated by 32P-postlabeling assay at 6, 18, 24, 36, and 48 hr postinjection. Peak levels of C8-AF were achieved at 18-36 hr post-injection in both rapid and slow acetylators. C8-AF levels were significantly higher in tumor-target organs (liver and urinary bladder) than in nontarget organs (heart, colon, and prostate). Significant differences in C8-AF levels between rapid and slow acetylators in liver, heart, colon, and prostate were not observed. However, C8-AF levels in urinary bladder were significantly (four-fold) higher in rapid versus slow acetylators. These results suggest that 2-aminofluorene forms significantly higher levels of DNA adducts in tumor-target organs than in non-target organs and that acetyltransferase polymorphism plays a significant role in 2-aminofluorene-DNA adduct formation in urinary bladder of Syrian hamster.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Animals
  • Cricetinae
  • DNA Adducts / biosynthesis*
  • DNA Adducts / drug effects
  • Fluorenes / pharmacology*
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Mesocricetus
  • Mutagens / pharmacology*
  • Urinary Bladder / drug effects*
  • Urinary Bladder / metabolism

Substances

  • DNA Adducts
  • Fluorenes
  • Mutagens
  • 2-aminofluorene