The Fenton degradation as a nonenzymatic model for microsomal denitrosation of N-nitrosodimethylamine

Chem Res Toxicol. Jul-Aug 1989;2(4):247-53. doi: 10.1021/tx00010a006.

Abstract

The microsomal metabolism of the carcinogen N-nitrosodimethylamine (NDMA) was suggested to be initiated by hydrogen atom abstraction to form an alpha-nitrosamino radical, which either oxidizes further to an alpha-hydroxy nitrosamine as the initial product of the activating dealkylation pathway or fragments to the nitric oxide radical and N-methylformaldimine as the first step of the presumably inactivating denitrosation route. To examine the chemistry of the alpha-nitrosamino radical in a nonenzymatic setting, we exposed NDMA to the Fenton reagent, which is known to be capable of abstracting hydrogen atoms from organic species. The products observed were those expected of a denitrosation model. Solutions containing 13 mM [14C]NDMA, 15 mM FeSO4, 15 mM H2O2, and 7.5 mM H2SO4 were kept at 4-10 degrees C for 1 h and then basified to yield methylamine (3.2 +/- 0.5 mM, mean +/- SD, n = 8), formaldehyde (3.1 +/- 0.9 mM), and unreacted nitrosamine (10.2 +/- 0.7 mM) as the only radioactive species detected, with total nitrate/nitrite also being found at a level of 2.8 +/- 0.5 mM. N-Methylformaldiminium ion was identified as an intermediate. The parallels between these results and those seen in the microsomal reaction support the hypothesis that the alpha-nitrosamino radical is a common intermediate in enzymatic denitrosation versus dealkylation of NDMA.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Catalysis
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 Enzyme System / metabolism
  • Dimethylnitrosamine / metabolism*
  • Imines / metabolism
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microsomes / metabolism*
  • Models, Biological
  • Nitroso Compounds / metabolism*

Substances

  • Imines
  • Nitroso Compounds
  • Cytochrome P-450 Enzyme System
  • Dimethylnitrosamine