N-sulfoöxy-2-aminofluorene is the major ultimate electrophilic and carcinogenic metabolite of N-hydroxy-2-acetylaminofluorene in the livers of infant male C57BL/6J x C3H/HeJ F1 (B6C3F1) mice.

The hepatic DNA of 12-day-old male B6C3F1 (C57BL/6J X C3H/HeJ) mice given an i.p. dose of 0.06 or 0.11 mumol/g body weight of N-hydroxy-[3H]-2-acetylaminofluorene (N-hydroxy-AAF) contained at 9 h approximately 3 or 6 pmol of N-(deoxyguanosin-8-yl)-2-aminofluorene adducts per mg. Together the level of the two acetylated adducts N-(deoxyguanosin-8-yl)-2-acetylaminofluorene and 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene was less than or equal to 10% of this amount. The same doses of unlabeled carcinogen induced by 10 months a 100% incidence of hepatomas with averages of 10 and 15 hepatomas per mouse, respectively. Injection of 0.04 mumol/g body weight of pentachlorophenol (PCP) 45 min before the dose of N-hydroxy-AAF decreased the number of adducts in the DNA by 90% and the average number of hepatomas per liver by 80-90%. As compared to their normal male littermates, male brachymorphic B6C3F2 mice, which are deficient in hepatic 3'-phosphoadenosine-5'-phosphosulfate (PAPS), treated with N-hydroxy-AAF formed only 25% as many hepatic DNA adducts and developed only 10% as many hepatomas. Hepatic cytosols from 12-day-old B6C3F1 mice contained PAPS-dependent sulfotransferase activity for N-hydroxy-2-aminofluorene (N-hydroxy-AF), a previously unrecognized activity, as well as sulfotransferase activity for N-hydroxy-AAF; both activities were inhibited 60% by 1 microM and greater than or equal to 80% by 10 microM PCP. Cytosolic acetyl coenzyme A-dependent acetyltransferase activity for N-hydroxy-AF, cytosolic N,O-acyltransferase activity for N-hydroxy-AAF, and microsomal deacetylase for N-hydroxy-AAF were not significantly inhibited by PCP under these conditions. The above data strongly indicate that N-sulfoöxy-2-aminofluorene is the major ultimate electrophilic and carcinogenic metabolite of N-hydroxy-AAF in the livers of infant male B6C3F1 mice.
AuthorsC C Lai, J A Miller, E C Miller, A Liem
JournalCarcinogenesis (Carcinogenesis) Vol. 6 Issue 7 Pg. 1037-45 (Jul 1985) ISSN: 0143-3334 [Print] UNITED STATES
PMID3860305 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Carcinogens
  • Tritium
  • Hydroxyacetylaminofluorene
  • DNA
  • 2-Acetylaminofluorene
  • Acyltransferases
  • Sulfurtransferases
  • 2-Acetylaminofluorene (analogs & derivatives)
  • Acyltransferases (metabolism)
  • Animals
  • Carcinogens (isolation & purification)
  • Crosses, Genetic
  • Cytosol (enzymology)
  • DNA (metabolism)
  • Female
  • Hydroxyacetylaminofluorene (metabolism)
  • Liver (enzymology, metabolism)
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Phenotype
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Strains
  • Sulfurtransferases (metabolism)
  • Tritium

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: