Dosimetry of N6-Formyllysine Adducts Following [13C2H2]-Formaldehyde Exposures in Rats

With formaldehyde as the major source of endogenous N-6-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 [(CH2)-C-15-H-2]-formaldehyde using liquid chromatography-coupled tandem mass spectrometry. Exogenous N-6-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 N-6-formyllysine being derived from exogenous sources. The results parallel previous studies of formaldehyde-induced DNA adducts.