Title: Molecular dosimetry of N2-hydroxymethyl-dG DNA adducts in rats exposed to formaldehyde.
Authors: Lu, Kun; Moeller, Benjamin; Doyle-Eisele, Melanie; McDonald, Jacob; Swenberg, James A
Published In Chem Res Toxicol, (2011 Feb 18)
Abstract: In this study, both endogenous and exogenous N(2)-hydroxymethyl-dG adducts in nasal DNA of rats exposed to 0.7, 2, 5.8, 9.1, or 15.2 ppm [(13)CD(2)] formaldehyde for 6 h were quantified by a highly sensitive nano-UPLC-MS/MS method. Our data clearly demonstrated that exogenous formaldehyde DNA adducts form in a highly nonlinear fashion, with a 21.7-fold increase in exposure causing a 286-fold increase in exogenous adducts. The ratio of exogenous/endogenous DNA adducts demonstrated that endogenous DNA adducts dominated at low exposures, comprising more than 99%. In contrast, exogenous adducts were not detectable in the bone marrow of rats exposed to 15.2 ppm [(13)CD(2)] formaldehyde.
PubMed ID: 21155545
MeSH Terms: Animals; Bone Marrow/drug effects; Chromatography, High Pressure Liquid/methods; DNA Adducts/analysis*; DNA Adducts/metabolism*; Formaldehyde/toxicity*; Guanine/analogs & derivatives; Nasal Mucosa/drug effects; Rats; Tandem Mass Spectrometry/methods*