Urinary 8-hydoxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) levels in Aldh2 knock-out mice under acetaldehyde exposure.
To clarify the carcinogenicity of acetaldehyde when associated with ALDH (aldehyde dehydrogenase) 2 polymorphism, Aldh2 knock-out (Aldh2-/-) mice and their wild type (Aldh2+/+) mice were exposed to two different concentrations of acetaldehyde (125 ppm and 500 ppm) for two weeks. Aldh2-/- mice, which have the same genetic background as C57BL/6J (wild mice) except for the Aldh2 gene, were used as models of humans who lack ALDH2 activity. Urinary 8-hydroxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) levels were measured as indicators of oxidative DNA damage and lipid peroxidation, respectively. At 125 ppm acetaldehyde exposure for 12 d, urinary 8-OHdG levels in Aldh2+/+ mice did not increase. However, urinary 8-OHdG levels in Aldh2-/- mice were slightly increased by the end of the exposure. On the other hand, plasma MDA levels did not increase in either Aldh2-/- orAldh2+/+ mice. At 500 ppm, urinary 8-OHdG levels in both Aldh2-/- and Aldh2+/+ mice significantly increased after 6 and 12 d, but there was no genetic difference. On the other hand, plasma MDA levels in Aldh2+/+ and Aldh2-/- mice did not increase at either 125 ppm or 500 ppm after two weeks of exposure. In conclusion, it is suspected that DNA was damaged by acetaldehyde inhalation, and that susceptibility to acetaldehyde varies according to Aldh2 genotype.
Ogawa
Masanori
M
Department of Environmental Health, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
Isse
Toyohi
T
Oyama
Tsunehiro
T
Kunugita
Naoki
N
Yamaguchi
Tetsunosuke
T
Kinaga
Tsuyoshi
T
Narai
Rie
R
Matsumoto
Akiko
A
Kim
Yong-Dae
YD
Kim
Heon
H
Uchiyama
Iwao
I
Kawamoto
Toshihiro
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000652:urine; D007564:Japan; D008297:Male; D008315:Malondialdehyde / Q000032:analysis* / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D011110:Polymorphism, Genetic
D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D000079:Acetaldehyde