Products formed from the in vitro reaction of metabolites of 3-aminochrysene with calf thymus DNA

Chem Biol Interact. 1993 Jan;86(1):1-15. doi: 10.1016/0009-2797(93)90107-a.

Abstract

3-Aminochrysene, a mutagenic geometric isomer of the mutagenic and carcinogenic aromatic amine 6-aminochrysene, has been synthesized and its metabolic activation studied by characterization of the products formed from the reaction of metabolites with calf thymus DNA. DNA adducts produced by 3-aminochrysene via N-oxidation were examined by preparing 3-nitrosochrysene and incubating the nitroso derivative with calf thymus DNA in the presence of ascorbic acid (to generate the N-hydroxy derivative) at pH 5. The major adduct, as determined by 1H-NMR and thermospray-mass spectrometry of the modified nucleoside obtained after enzymatic hydrolysis of the modified DNA, was N-(deoxyguanosin-8-yl)-3-aminochrysene. Thus, the reaction of N-hydroxy-3-aminochrysene with DNA differs from that of N-hydroxy-6-aminochrysene, which had previously been shown to generate N-(deoxyguanosin-8-yl)-6-aminochrysene, 5-(deoxyguanosin-N2-yl)-6-aminochrysene and N-(deoxyinosin-8-yl)-6- aminochrysene as major adducts. 32P-Postlabeling analysis of DNA treated with 3-aminochrysene in the presence of liver microsomes from rats pretreated with phenobarbital indicated an adduct pattern identical to that seen with DNA that had been treated with 3-nitrosochrysene and ascorbic acid. However, DNA treated with 3-aminochrysene (3-AC) in the presence of liver microsomes from rats pretreated with 3-methylcholanthrene contained a major adduct that was chromatographically distinct from N-(deoxyguanosin-8-yl)-3-aminochrysene.

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology
  • Biotransformation
  • Cattle
  • Chrysenes / metabolism*
  • Chrysenes / pharmacology
  • DNA / drug effects
  • DNA / metabolism*
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Microsomes, Liver / metabolism
  • Mutagenicity Tests
  • Mutagens / metabolism*
  • Nitroso Compounds / metabolism*
  • Nitroso Compounds / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Thymus Gland / chemistry*

Substances

  • Chrysenes
  • Mutagens
  • Nitroso Compounds
  • 3-nitrosochrysene
  • 3-aminochrysene
  • DNA
  • Ascorbic Acid