Molecular Dosimetry of N2-Hydroxymethyl-dG DNA Adducts in Rats Exposed to Formaldehyde

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 [(CD2)-C-13] formaldehyde for 6 h were quantified by a highly sensitive nano-UPLC-MS/MS method. Our data dearly 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 [(CD2)-C-13] formaldehyde.