N6-Formyllysine as a Biomarker of Formaldehyde Exposure: Formation and Loss of N6-Formyllysine in Nasal Epithelium in Long-Term, Low-Dose Inhalation Studies in Rats

Chem Res Toxicol. 2017 Aug 21;30(8):1572-1576. doi: 10.1021/acs.chemrestox.7b00075. Epub 2017 Jul 27.

Abstract

Exposure to both endogenous and exogenous formaldehyde has been established to be carcinogenic, likely by virtue of forming nucleic acid and proteins adducts such as N6-formyllysine. To better assess N6-formyllysine as a biomarker of formaldehyde exposure, we studied accumulation of N6-formyllysine adducts in tissues of rats exposed by inhalation to 2 ppm [13C2H2]-formaldehyde for 7, 14, 21, and 28 days (6 h/day) and investigated adduct loss over a 7-day postexposure period using liquid chromatography-coupled tandem mass spectrometry. Our results showed formation of exogenous adducts in nasal epithelium and to some extent in trachea but not in distant tissues of lung, bone marrow, or white blood cells, with a 2-fold increase over endogenous N6-formyllysine over a 3-week exposure period. Postexposure analyses indicated a biexponential decay of N6-formyllysine in proteins extracted from different cellular compartments, with half-lives of ∼25 and ∼182 h for the fast and slow phases, respectively, in cytoplasmic proteins. These results parallel the behavior of DNA adducts and DNA-protein cross-links, with protein adducts cleared faster than DNA-protein cross-links, and point to the potential utility of N6-formyllysine protein adducts as biomarkers of formaldehyde.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Biomarkers / chemistry
  • Bone Marrow / chemistry
  • Bone Marrow / metabolism
  • Carbon Isotopes / chemistry
  • Chromatography, High Pressure Liquid
  • DNA Adducts / analysis
  • Formaldehyde / chemistry
  • Formaldehyde / toxicity*
  • Half-Life
  • Inhalation Exposure
  • Leukocytes / chemistry
  • Leukocytes / metabolism
  • Lung / chemistry
  • Lung / metabolism
  • Lysine / analogs & derivatives*
  • Lysine / analysis*
  • Male
  • Nasal Mucosa / chemistry
  • Nasal Mucosa / drug effects*
  • Nasal Mucosa / metabolism
  • Proteins / chemistry
  • Proteins / metabolism
  • Rats
  • Rats, Inbred F344
  • Tandem Mass Spectrometry
  • Time Factors

Substances

  • Biomarkers
  • Carbon Isotopes
  • DNA Adducts
  • Proteins
  • N(epsilon)-formyllysine
  • Formaldehyde
  • Lysine