Ethanol Consumption Inhibits Fetal DNA Methylation in Mice: Implications for the Fetal Alcohol Syndrome

Authors

  • Anthony J. Garro,

    Corresponding author
    1. University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey
    2. Alcohol Research and Treatment Center, The Department of Veterans Affairs Medical Center, Bronx, New York
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  • Dani L. McBeth,

    1. City University of New York Medical School/Sophie Davis School of Biomedical Education of the City College of New York, New York, New York
    2. Alcohol Research and Treatment Center, The Department of Veterans Affairs Medical Center, Bronx, New York
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  • Viera Lima,

    1. City University of New York Medical School/Sophie Davis School of Biomedical Education of the City College of New York, New York, New York
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  • Charles S. Lieber

    1. Alcohol Research and Treatment Center, The Department of Veterans Affairs Medical Center, Bronx, New York
    2. Mt. Sinai School of Medicine, City University of New York, New York, New York.
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  • This research was supported by the March of Dimes Birth Defects Foundation, Reproductive Hazards in the Workplace, Home, Community and Environment Grant 15-155, The City University of New York PSC/CUNY Research Awards Program, The Veterans Administration and Grants AA 03509, RR03060, and 2 SO7-RR07132 from the Department of Health and Human Services.

Reprint requests: Dr. Anthony J. Garro, Department of Microbiology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103.

Abstract

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 μM, 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.

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