Acute ethanol exposure suppresses the repair of O6-methylguanine DNA lesions in castrated adult male rats.
Alcohol has clearly been associated with an increase of cancers in numerous tissue, including the respiratory tract, colon, rectum, liver, but especially the esophagus, larynx, pharynx, and mouth. Alcohol alone has not been shown to be a mutagen until it is converted to acetaldehyde and, therefore, alcohol presumably acts as a cocarcinogen. Previous data has shown that alcohol concentrations of 2% or greater inhibits DNA repair, and in light of the widespread consumption of alcoholic beverages with alcohol contents ranging from 4 to 5% (beer and wine coolers) to 50% (whiskey), interest in determining the mechanism(s) responsible for alcohol-induced carcinogenesis has heightened. Although previous studies, in intact rats, have investigated the effects of chronic alcohol exposure on some aspects of DNA repair, we have begun to address the effects of acute or "binge" alcohol exposure on mammalian DNA repair. Toward this end, we report the inhibition of O6-methylguanine-DNA methyltransferase (MGMT) by a single intraperitoneal injection of 30% ethanol in adult male castrated rats. This inhibition lasted for at least 24 hr. We also observed a dose-response effect of ethanol on MGMT activity, again only in the castrated rats. The finding of ethanol's effect on MGMT activity in castrated and not intact rats implies a hormonal component of MGMT DNA repair response, which has only been alluded to in past research.
Wilson
D M
DM
Department of Pediatrics, Riley Hospital, Indianapolis, IN 46202.
Tentler
J J
JJ
Carney
J P
JP
Wilson
T M
TM
Kelley
M R
MR
D000818:Animals; D003043:Cocarcinogenesis; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D019853:O(6)-Methylguanine-DNA Methyltransferase; D009919:Orchiectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D006147:Guanine; C008449:O-(6)-methylguanine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase