8-Aminoguanine: a base modification produced in rat liver nucleic acids by the hepatocarcinogen 2-nitropropane

Chem Res Toxicol. 1993 May-Jun;6(3):269-76. doi: 10.1021/tx00033a004.


2-Nitropropane (2-NP), an important industrial chemical and a hepatocarcinogen in rats, had previously been found to produce several modifications of nucleosides in rat liver RNA and DNA that are discernible using HPLC with electrochemical detection. While one of these modifications has been identified as an increase in the levels of 8-oxoguanosine and 8-oxo-2'-deoxyguanosine in RNA and DNA, respectively, the others had not been identified. We now present evidence that a major modification in rat liver nucleic acids due to the administration of 2-NP is the amination of guanine at C8, apparently a completely novel in vivo reaction. 8-Aminoguanosine, isolated from hydrolysates of liver RNA from 2-NP-treated rats, cochromatographed with synthetic or commercially-obtained standard on reverse-phase as well as cation-exchange HPLC, and its UV spectral characteristics at acidic, neutral, and basic pH were identical to those of the standard. Acid hydrolysis produced 8-aminoguanine, which had a retention time and fragmentation pattern identical to that of the standard on gas chromatography-mass spectrometry of the trimethylsilyl derivatives. Evidence for the presence of 8-aminodeoxyguanosine in liver DNA of rats treated with 2-NP was also obtained by cochromatography with synthetic standard on HPLC. Hydroxylamine-O-sulfonic acid was found to react with RNA and DNA to give 8-oxo- and 8-amino-substituted guanines. We propose, as a working hypothesis, that 2-NP may be metabolized to hydroxylamine-O-sulfonate or acetate, which yield the reactive nitrenium ion, NH2+, capable of aminating cellular macromolecules in vivo.

Publication types

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

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Base Composition / drug effects
  • Carcinogens / toxicity*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / chemistry
  • Deoxyguanosine / metabolism
  • Guanine / analogs & derivatives*
  • Guanine / chemistry
  • Guanine / metabolism
  • Guanosine / analogs & derivatives
  • Guanosine / chemistry
  • Guanosine / metabolism
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Nitroparaffins / toxicity*
  • Propane / analogs & derivatives*
  • Propane / toxicity
  • Purine-Nucleoside Phosphorylase / antagonists & inhibitors*
  • Rats
  • Rats, Inbred F344


  • Carcinogens
  • Nitroparaffins
  • Guanosine
  • 8-aminoguanine
  • 8-aminoguanosine
  • Guanine
  • 8-Hydroxy-2'-Deoxyguanosine
  • Purine-Nucleoside Phosphorylase
  • Deoxyguanosine
  • 2-nitropropane
  • Propane