ETHANOL-CONSUMPTION INHIBITS FETAL DNA METHYLATION IN MICE - IMPLICATIONS FOR THE FETAL ALCOHOL SYNDROME
ETHANOL-CONSUMPTION INHIBITS FETAL DNA METHYLATION IN MICE - IMPLICATIONS FOR THE FETAL ALCOHOL SYNDROME
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DOI：
10.1111/j.1530-0277.1991.tb00536.x
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发表时间：
1991-06-01
影响因子：
3.2
通讯作者：
LIEBER, CS
中科院分区：
文献类型：
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作者：
GARRO, AJ;MCBETH, DL;LIEBER, CS
从妊娠第9天至第11天，给孕鼠急性给予乙醇(3g/kg，每天2次)，可导致胎儿脱氧核糖核酸(DNA)甲基化。从乙醇处理的小鼠胚胎中分离出的细胞核，即使在过量的S-腺苷蛋氨酸的存在下，甲基酶活性也低于对照组，腺苷蛋氨酸是DNA甲基转移酶的甲基供体。乙醛在体外可抑制DNA甲基转移酶的活性，浓度低至3-10mU-M。由于DNA甲基化被认为在胚胎发育过程中对基因表达起着重要的调节作用，与酒精相关的胎儿DNA甲基化改变可能导致胎儿酒精综合征的发育异常。
Acute ethanol administration (3 g/kg twice a day) to pregnant mice, from the 9th thru the 11th day of gestation, resulted in hypomethylation of fetal deoxyribonucleic acid (DNA). Nuclei isolated from the fetuses of the ethanol-treated mice had lower levels of methylase activity relative to controls even in the presence of excess S-adenosylmethionine, which serves as the methyl donor for the enzyme DNA methyltransferase. Acetaldehyde, at concentrations as low as 3 to 10-mu-M, inhibited DNA methyltransferase activity in vitro. Since DNA methylation is thought to play an important role in the regulation of gene expression during embryogenesis, ethanol-associated alterations in fetal DNA methylation may contribute to the developmental abnormalities seen in the fetal alcohol syndrome.