Effects of acetaldehyde inhalation in mitochondrial aldehyde dehydrogenase deficient mice (Aldh2-/-)

Front Biosci (Elite Ed). 2010 Jun 1;2:1344-54. doi: 10.2741/e194.

Abstract

Human body might be exposed to acetaldehyde from smoking or occupational environment, which is known to be associated with cancer through the formation of DNA adducts, in particular, N2-ethylidene-2'- deoxyguanosine (N2-ethylidene-dG). Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that contribute to the detoxification of acetaldehyde in human body. In this study, wild type (Aldh2+/+) and Aldh2KO (Aldh2-/-) mice were exposed to the air containing 0, 125, 500 ppm acetaldehyde for 2 weeks. After inhalation, levels of N2- ethylidene-dG in the chromosomal DNA were analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS). N2-ethylidene-dG levels in livers of Aldh2-/- mice were always lower than those of Aldh2+/+ mice, suggesting that Aldh2 deficiency might cause the induction of acetaldehyde metabolizing enzymes in the liver such as P450s. The differences between Aldh2-/- and Aldh2+/+ mice were greater in the order of nasal epithelium > lung > dorsal skin, suggesting that nasal epithelium and lung are the major target sites for acetaldehyde. Acetaldehyde inhalation may cause a high risk in nasal epithelium and lung cancers for individuals with inactive ALDH2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaldehyde / administration & dosage*
  • Acetaldehyde / blood
  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase / metabolism*
  • Animals
  • Body Weight
  • DNA Adducts / metabolism
  • Inhalation Exposure
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout

Substances

  • DNA Adducts
  • Aldehyde Dehydrogenase
  • Acetaldehyde