Effects of acetaldehyde inhalation in mitochondrial aldehyde dehydrogenase deficient mice (Aldh2-/-).
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.
Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan. oyama@med.uoeh-u.ac.jp
Tsunehiro
T
Oyama
Haruna
H
Nagayoshi
Tomonari
T
Matsuda
Megumi
M
Oka
Toyohi
T
Isse
Hsu-Sheng
HS
Yu
Thi-Thu-Phuong
TT
Pham
Masayuki
M
Tanaka
Norio
N
Kagawa
Kazuhiro
K
Kaneko
Toshihiro
T
Kawamoto
D000079:Acetaldehyde / Q000008:administration & dosage* / Q000097:blood; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D018736:DNA Adducts / Q000378:metabolism; D019570:Inhalation Exposure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D018736:DNA Adducts; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde