[Frontiers in Bioscience E2, 1344-1354, June 1, 2010]

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

Tsunehiro Oyama, Tsunehiro Oyama1, Haruna Nagayoshi2,3, Tomonari Matsuda2, Megumi Oka2, Toyohi Isse4, Hsu-Sheng Yu1, Thi-Thu-Phuong Pham1, Masayuki Tanaka1, Norio Kagawa5, Kazuhiro Kaneko6, Toshihiro Kawamoto1

1Departments of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, 807-8555, Japan, 2Research Center for Environmental Quality Management, Kyoto University, Otsu, Shiga, 520-0811, Japan, 3Osaka Prefectural Institute of Public Health, Osaka, 537-0025, Japan, 4Section of Postgraduate Guidance, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, 807-8555, Japan, 5Global COE, Nagoya University School of Medicine, Nagoya, Aichi, 466-8550, Japan,6Division of Digestive Endoscopy/Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Wild type (Aldh2+/+ mice) and Aldh2KO mice (Aldh2-/- mice)
3.2. Treatments
3.3. Blood acetaldehyde concentration
3.4. DNA isolation from mouse organs
3.5. DNA digestion
3.6. Instrumentation
3.7. Statistics
4. Results
4.1. Blood acetaldehyde concentration and body weight from the previous report
4.2. DNA adduct levels in mice target organs treated with acetaldehyde inhalation
5. Discussion
6. Acknowledgements
7. References

1. 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.