Dosimetry of N[superscript 6]-Formyllysine Adducts Following [[superscript 13]C[superscript 2]H[subscript 2]]-Formaldehyde Exposures in Rats

Abstract

With formaldehyde as the major source of endogenous N[superscript 6]-formyllysine protein adducts, we quantified endogenous and exogenous N[superscript 6]-formyllysine in the nasal epithelium of rats exposed by inhalation to 0.7, 2, 5.8, and 9.1 ppm [[superscript 13]C[superscript 2]H[subscript 2]]-formaldehyde using liquid chromatography-coupled tandem mass spectrometry. Exogenous N[superscript 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[superscript 6]-formyllysine being derived from exogenous sources. The results parallel previous studies of formaldehyde-induced DNA adducts.