Dosimetry of N⁶-formyllysine adducts following [¹³C²H₂]-formaldehyde exposures in rats

Chem Res Toxicol. 2013 Oct 21;26(10):1421-3. doi: 10.1021/tx400320u. Epub 2013 Oct 10.

Abstract

With formaldehyde as the major source of endogenous N⁶-formyllysine protein adducts, we quantified endogenous and exogenous N⁶-formyllysine in the nasal epithelium of rats exposed by inhalation to 0.7, 2, 5.8, and 9.1 ppm [¹³C²H₂]-formaldehyde using liquid chromatography-coupled tandem mass spectrometry. Exogenous N⁶-formyllysine was detected in the nasal epithelium, with concentration-dependent formation in total as well as fractionated (cytoplasmic, membrane, nuclear) proteins, but was not detected in the lung, liver, or bone marrow. Endogenous adducts dominated at all exposure conditions, with a 6 h 9.1 ppm formaldehyde exposure resulting in one-third of the total load of N⁶-formyllysine being derived from exogenous sources. The results parallel previous studies of formaldehyde-induced DNA adducts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Isotopes / chemistry
  • Chromatography, High Pressure Liquid
  • Formaldehyde / chemistry*
  • Formaldehyde / toxicity
  • Inhalation Exposure
  • Lysine / analysis*
  • Lysine / chemistry
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / metabolism
  • Radiometry
  • Rats
  • Tandem Mass Spectrometry*
  • Time Factors

Substances

  • Carbon Isotopes
  • Membrane Proteins
  • Formaldehyde
  • Lysine