Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome.
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.
Garro
A J
AJ
Department of Microbiology, UMDNJ-New Jersey Medical School, Newark 07103.
McBeth
D L
DL
Lima
V
V
Lieber
C S
CS
D044503:5-Methylcytosine; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics*; D004252:DNA Mutational Analysis; D015257:DNA-Cytosine Methylases / Q000037:antagonists & inhibitors* / Q000502:physiology; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000201:enzymology* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D011247:Pregnancy
D044503:5-Methylcytosine; D003596:Cytosine; D015257:DNA-Cytosine Methylases