• DOI:10.1021/TX00039A011
• Corpus ID: 25529069

Activation of the liver carcinogen 2-nitropropane by aryl sulfotransferase.

@article{Sodum1994ActivationOT,
  title={Activation of the liver carcinogen 2-nitropropane by aryl sulfotransferase.},
  author={Rama S. Sodum and Ock Soon Sohn and Guo-ming Nie and Emerich S. Fiala},
  journal={Chemical research in toxicology},
  year={1994},
  volume={7 3},
  pages={
          344-51
        }
}

• R. Sodum, O. Sohn, +1 author E. Fiala
• Published 1 May 1994
• Biology, Chemistry
• Chemical research in toxicology

8-Aminoguanine had previously been identified as one of the nucleic acid base modifications produced in livers of rats by treatment with the hepatocarcinogen 2-nitropropane (2-NP), and a hypothetical mechanism of activation of 2-NP to hydroxylamine-O-sulfonate or acetate that would lead to NH2+, an aminating species, was proposed [Sodum et al. (1993) Chem. Res. Toxicol. 6, 269-276]. We now present in vivo and in vitro experimental evidence for the activation of 2-NP to an aminating species by rat liver aryl sulfotransferase. Pretreatment of rats with the aryl sulfotransferase inhibitors pentachlorophenol or 2,6-dichloro-4-nitrophenol significantly decreased the levels of liver nucleic acid modifications produced by 2-NP treatment. Furthermore, partially purified rat liver aryl sulfotransferase was shown to activate 2-NP and 2-NP nitronate in vitro at neutral pH and 37 degrees C, to a reactive species that aminated guanosine at the C8 position. This activation was dependent on the presence of the enzyme, its specific cofactor adenosine 3'-phosphate 5'-phosphosulfate, and mercaptoethanol. As in the case of the in vitro studies, pentachlorophenol and 2,6-dichloro-4-nitrophenol inhibited the in vitro formation of 8-aminoguanosine and 8-oxoguanosine. The corresponding primary nitroalkane, 1-nitropropane, which is not mutagenic and does not appear to be carcinogenic, was not a substrate for aryl sulfotransferase in the in vitro amination of guanosine.