Effect of ethanol ingestion and acetaldehyde on oxygen(6)-methylguanine transferase (O(6) MeGT).
Item
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Title
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Effect of ethanol ingestion and acetaldehyde on oxygen(6)-methylguanine transferase (O(6) MeGT).
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Identifier
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AAI8820858
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identifier
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8820858
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Creator
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Espina, Noel Garcia.
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Contributor
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Adviser: Anthony J. Garro
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Date
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1988
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Biochemistry
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Abstract
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Heavy alcohol consumption is one of several dietary factors which have been linked epidemiologically to an increased risk of cancer. One possible mechanism by which alcohol abuse might lead to an increased risk of cancer is to inhibit the repair of carcinogen-DNA adducts thereby increasing the number of somatic mutations associated with carcinogen exposure. The results presented here show that chronic ethanol consumption leads to a decreased capacity for repair of dimethylnitrosamine induced alkylation at the O{dollar}\sp6{dollar} position of guanine. O{dollar}\sp6{dollar}-methylguanine transferase (O{dollar}\sp6{dollar}MeGT) activity is decreased following both chronic and acute ethanol administration. This in vivo decrease in O{dollar}\sp6{dollar}MeGT activity is primarily due to acetaldehyde, the reactive metabolite, that is generated during ethanol metabolism. In vitro, rat and human O{dollar}\sp6{dollar}MeGT are inhibited by acetaldehyde at 0.01-1.0uM concentrations. Ethanol at 10-50mM concentrations also inhibited O{dollar}\sp6{dollar}MeGT. These concentrations are physiologically significant in that these alcohol and acetaldehyde levels are found in blood of alcoholics or animals fed ethanol. Although a direct effect cannot be ruled out, the in vitro inhibitory effect of ethanol may be due to trace levels of acetaldehyde that is generated spontaneously or produced from residual alcohol dehydrogenase activity. The in vivo and in vitro inhibitory effect on O{dollar}\sp6{dollar}MeGT, mediated through its metabolite acetaldehyde, may contribute to ethanol's capacity to act as a cocarcinogen.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
