8-AMINOGUANINE - A BASE MODIFICATION PRODUCED IN RAT-LIVER NUCLEIC-ACIDS BY THE HEPATOCARCINOGEN 2-NITROPROPANE

2-Nitropropane (2-NP), an important industrial chemical and a hepatoca rcinogen in rats, had previously been found to produce several modific ations of nucleosides in rat liver RNA and DNA that are discernible us ing HPLC with electrochemical detection. While one of these modificati ons has been identified as an increase in the levels of 8-oxoguanosine and 8-oxo-2'-deoxguanosine in RNA and DNA, respectively, the others h ad not been identified. We now present evidence that a major modificat ion in rat liver nucleic acids due to the administration of 2-NP is th e amination of guanine at C8, apparently a completely novel in vivo re action. 8-Aminoguanosine, isolated from hydrolysates of liver RNA from 2-NP-treated rats, cochromatographed with synthetic or commercially-o btained 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-aminog uanine, which had a retention time and fragmentation pattern identical to that of the standard on gas chromatography-mass spectrometry of th e trimethylsilyl derivatives. Evidence for the presence of 8-aminodeox y-guanosine in liver DNA of rats treated with 2-NP was also obtained b y cochromatography with synthetic standard on HPLC. Hydroxylamine-O-su lfonic acid was found to react with RNA and DNA to give 8-oxo- and 8-a mino-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.