Evaluation of effects of aldehyde dehydrogenase on oxidative stress

醛脱氢酶-2 （ALDH2）将乙醇产生的乙醛代谢成乙酸，并在体内乙醛氧化中起主要作用。一半的日本人有不活跃的ALDH2。为了研究乙醛的致突变性，在体内对暴露于乙醛或乙醇的Aldh2 KO小鼠和野生型（Aldh2 WT）小鼠进行了微核（MN）测定和T细胞受体（TCR）基因突变测定。我们还观察了尿中8-羟基-2'-脱氧鸟苷（8-OHdG）、血红蛋白相关乙醛（Hb-AA）和线粒体DNA tRNA基因突变。结果显示，Aldh2 KO小鼠暴露于乙醛后网状细胞微核频率显著增加，而Aldh2 WT小鼠则没有。此外，即使在对照组中，Aldh2 KO小鼠尿液中微核、TCR突变和8-OHdG水平的频率也显著高于Aldh2 WT小鼠。这些结果表明，Aldh2不仅在乙醛解毒中起重要作用，而且在小鼠的氧化应激中也起重要作用。

Aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde produced from ethanol into acetate and plays a major role in the oxidation of acetaldehyde in vivo. Half of Japanese have inactive ALDH2. In order to investigate the mutagenicity of acetaldehyde, micronucleus (MN) assay and T cell receptor (TCR) gene mutation assay were performed in Aldh2 KO mice and wild type (Aldh2 WT) mice exposed to acetaldehyde or ethanol in vivo. We also observed the urine 8-hydroxy-2'-deoxyguanosine (8-OHdG), hemoglobin-associated acetaldehyde (Hb-AA), and mutation on tRNA gene of mitochondrial DNA. In results, frequencies of micronuclei in reticulocytes significantly increased by acetaldehyde exposure in Aldh2 KO mice, but not in Aldh2 WT mice. In addition, frequencies of micronuclei, TCR mutation, and 8-OHdG levels in urine were significantly high in Aldh2 KO mice than in Aldh2 WT mice even in control groups. These results indicate that Aldh2 plays a major role not only in acetaldehyde detoxification but also in oxidative stress in mice.