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

  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},
  volume={7 3},
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… 
Slow oxidation of acetoxime and methylethyl ketoxime to the corresponding nitronates and hydroxy nitronates by liver microsomes from rats, mice, and humans.
The observed results show that formation of sec-nitronates from ketoximes occurs slowly, but is not the only pathway involved in the oxidative biotransformation of these compounds.
Human phenol sulfotransferases hP-PST and hM-PST activate propane 2-nitronate to a genotoxicant.
Investigating the genotoxicity of P2N in various V79-derived cell lines engineered for expression of individual forms of human sulfotransferases shows that the human phenol sulfotranferases P-P ST and M-PST are capable of metabolically activating P2n and that the underlying mechanism is apparently identical to that resulting in the activation of P1N in rat liver, where 2-NP causes carcinomas.
Bioactivation of mutagens via sulfation
  • H. Glatt
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1997
Sulfation is a common final step in the biotransformation of xenobiotics and is traditionally associated with inactivation. However, the sulfate group is electron‐withdrawing and may be cleaved off
Toxicity and metabolism of nitroalkanes and substituted nitroalkanes.
The toxicological profiles, especially as related to events occurring during metabolism and biotransformation, which contribute to toxicological end points of established nitroaliphatic compounds are reviewed.
Enzymatic aspects of the phenol (aryl) sulfotransferases*
The presentation aims to provide an overview of the wealth of phenol sulfotransferases that are available for study but concentrates on the enzymology of rat and human enzymes, particularly on the predominant phenol sulfur sulfotranferase from rat liver.