Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome

• Published in: Alcoholism, clinical and experimental research Vol. 15; no. 3; p. 395
• Main Authors: Garro, A J, McBeth, D L, Lima, V, Lieber, C S
• Format: Journal Article
• Language: English
• Published: England 01.06.1991
• Subjects: 5-Methylcytosine; Animals; Cell Differentiation - genetics; Cytosine - analogs & derivatives; Cytosine - metabolism; DNA Damage - genetics; DNA Mutational Analysis; DNA-Cytosine Methylases - antagonists & inhibitors; DNA-Cytosine Methylases - physiology; Female; Fetal Alcohol Spectrum Disorders - enzymology; Fetal Alcohol Spectrum Disorders - genetics; Gene Expression Regulation - physiology; Mice; Pregnancy
• ISSN: 0145-6008
• DOI: 10.1111/j.1530-0277.1991.tb00536.x

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 microM, 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.