Chronic ethanol feeding alters hepatocyte memory which is not altered by acute feeding.
BACKGROUND
Gene expression changes in the liver after acute binge drinking may differ from the changes seen in chronic ethanol feeding in the rat. The changes in gene expression after chronic ethanol feeding may sensitize the liver to alcohol-induced liver damage, which is not seen after acute binge drinking.


METHODS
To test this hypothesis, gene microarray analysis was performed on the livers of rats (n = 3) fed an acute binge dose of ethanol (6 g/kg body wt) and killed at 3 and 12 hours after ethanol by gavage. The gene microarrays were compared with those made on the liver of rats from a previous study, in which the rats were fed ethanol by intragastric tube for 1 month (36% of calories derived from ethanol).


RESULTS
Microarray analysis data varied between the acute and chronic models in several important respects. Growth factors increased mainly in the chronic alcohol fed rat. Changes in enzymes involved in oxidative stress were noted only with chronic ethanol feeding. Gene expression of fat metabolism was increased only with chronic ethanol feeding. Most importantly, epigenetic related enzymes and acetylation and methylation of histones changed only after chronic ethanol feeding.


CONCLUSIONS
The results support the concept that chronic ethanol ingestion induces altered gene expression as a result of changes in epigenetic mechanisms, where acetylation and methylation of histones were altered.
Bardag-Gorce
F
F
Department of Pathology, Harbor-UCLA Medical Center, Torrance, California 90509, USA.
Oliva
Joan
J
Dedes
Jennifer
J
Li
Jun
J
French
Barbara A
BA
French
Samuel W
SW
D000107:Acetylation / Q000187:drug effects; D000208:Acute Disease; D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008745:Methylation / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D000431:Ethanol