Molecular dosimetry of N2-hydroxymethyl-dG DNA adducts in rats exposed to formaldehyde

Chem Res Toxicol. 2011 Feb 18;24(2):159-61. doi: 10.1021/tx1003886. Epub 2010 Dec 14.

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.

Publication types

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

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*

Substances

  • DNA Adducts
  • Formaldehyde
  • Guanine