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Effects of acetaldehyde inhalation in mitochondrial aldehyde dehydrogenase deficient mice (Aldh2-/-)
Tsunehiro Oyama1,Haruna Nagayoshi1,Tomonari Matsuda1,Megumi Oka1,Toyohi Isse1,Hsu-Sheng Yu1,Thi-Thu-Phuong Pham1,Masayuki Tanaka1,Norio Kagawa1,Kazuhiro Kaneko1,Toshihiro Kawamoto1
1
Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan. oyama@med.uoeh-u.ac.jp
DOI: 10.2741/E194 Volume 2 Issue 4, pp.1344-1354
Published: 01 June 2010
(This article belongs to the Special Issue Gene regulation and structure-function of P450 Cold stress response)
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.

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Tsunehiro Oyama, Haruna Nagayoshi, Tomonari Matsuda, Megumi Oka, Toyohi Isse, Hsu-Sheng Yu, Thi-Thu-Phuong Pham, Masayuki Tanaka, Norio Kagawa, Kazuhiro Kaneko, Toshihiro Kawamoto. Effects of acetaldehyde inhalation in mitochondrial aldehyde dehydrogenase deficient mice (Aldh2-/-). Frontiers in Bioscience-Elite. 2010. 2(4); 1344-1354.