In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O6-methylguanine transferase

Human and rat O6-methylguanine transferase (O6MeGT) are inhibited in vitro by ethanol at concentrations of 10 to 50 mM and by acetaldehyde, the first metabolite of ethanol, at concentrations as low as 0.01 microM. Several other enzymes, including glyceraldehyde-3-phosphate dehydrogenase and yeast al...

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Bibliographic Details
Published inCarcinogenesis (New York) Vol. 9; no. 5; p. 761
Main Authors Espina, N, Lima, V, Lieber, C S, Garro, A J
Format Journal Article
LanguageEnglish
Published England 01.05.1988
Subjects
Acetaldehyde - pharmacology
Animals
Disulfiram - pharmacology
Ethanol - pharmacology
Humans
In Vitro Techniques
Methyltransferases - antagonists & inhibitors
O-Methylguanine-DNA Methyltransferase
Rats
Rats, Inbred Strains
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Summary:Human and rat O6-methylguanine transferase (O6MeGT) are inhibited in vitro by ethanol at concentrations of 10 to 50 mM and by acetaldehyde, the first metabolite of ethanol, at concentrations as low as 0.01 microM. Several other enzymes, including glyceraldehyde-3-phosphate dehydrogenase and yeast alcohol dehydrogenase, which like O6MeGT have cysteines in their active sites, were not inhibited by acetaldehyde at the levels that inhibited O6MeGT. Disulfiram, an acetaldehyde dehydrogenase inhibitor, enhanced the inhibitory effect of ethanol in vivo. These results indicate that the inhibitory effect of ethanol on O6MeGT activity is mediated primarily via its metabolite, acetaldehyde.
ISSN:0143-3334
DOI:10.1093/carcin/9.5.761