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dc.contributor.authorNavasumrit, P
dc.contributor.authorMargison, Geoffrey P
dc.contributor.authorO'Connor, Peter J
dc.date.accessioned2009-11-10T10:22:34Z
dc.date.available2009-11-10T10:22:34Z
dc.date.issued2001
dc.identifier.citationEthanol modulates rat hepatic DNA repair functions., 36 (5):369-76 Alcohol Alcohol.en
dc.identifier.issn0735-0414
dc.identifier.pmid11524300
dc.identifier.urihttp://hdl.handle.net/10541/85757
dc.description.abstractTo further explore how ethanol may act at the DNA level, studies have been made of DNA repair mechanisms in male Wistar rats given ethanol either as an acute intragastric dose (5 g/kg) or continuously in a liquid diet (5% w/v) to provide 36% of the caloric intake. These treatments generate significant levels of free radicals with evidence of damage to DNA. The acute ethanol dose significantly inhibited O(6)-alkylguanine-DNA alkyltransferase (ATase) activity by 21-32% throughout the 24-h post-treatment period and this was confirmed by immunohistochemical detection of the ATase protein in hepatic nuclei. Twelve hours after the ethanol treatment, the activities of the DNA glycosylases, alkylpurine-DNA-N-glycosylase (APNG) and 8-oxoguanine-DNA glycosylase (OXOG glycosylase) were each increased by approximately 44%. In contrast, when given chronically via the liquid diet, ethanol initially had no effect on ATase activity, but after 4 weeks ATase activity was increased by 40%. Following ethanol withdrawal, ATase activity remained elevated for at least 12 h, but, by 24 h, the activity had fallen to the uninduced control level. DNA glycosylase activities were again affected differently. After 1 week of dietary ethanol exposure, there was no effect on APNG activity but it was inhibited by 19% at 4 weeks. OXOG glycosylase activity, on the other hand, was increased by 53% after 1 week, but decreased by 40% after 4 weeks. Although some of these changes in DNA repair capacity were relatively small, over time, their potential impact on the repair of endogenous or exogenous alkylation and/or oxidation damage in DNA would be substantial. These studies indicate possible mechanisms for the co-carcinogenic effects of ethanol.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshCentral Nervous System Depressants
dc.subject.meshDNA Glycosylases
dc.subject.meshDNA Repair
dc.subject.meshDNA-Formamidopyrimidine Glycosylase
dc.subject.meshEnzyme Activation
dc.subject.meshEthanol
dc.subject.meshLiver
dc.subject.meshMale
dc.subject.meshN-Glycosyl Hydrolases
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase
dc.subject.meshRats
dc.subject.meshRats, Wistar
dc.titleEthanol modulates rat hepatic DNA repair functions.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK.en
dc.identifier.journalAlcohol and Alcoholismen
html.description.abstractTo further explore how ethanol may act at the DNA level, studies have been made of DNA repair mechanisms in male Wistar rats given ethanol either as an acute intragastric dose (5 g/kg) or continuously in a liquid diet (5% w/v) to provide 36% of the caloric intake. These treatments generate significant levels of free radicals with evidence of damage to DNA. The acute ethanol dose significantly inhibited O(6)-alkylguanine-DNA alkyltransferase (ATase) activity by 21-32% throughout the 24-h post-treatment period and this was confirmed by immunohistochemical detection of the ATase protein in hepatic nuclei. Twelve hours after the ethanol treatment, the activities of the DNA glycosylases, alkylpurine-DNA-N-glycosylase (APNG) and 8-oxoguanine-DNA glycosylase (OXOG glycosylase) were each increased by approximately 44%. In contrast, when given chronically via the liquid diet, ethanol initially had no effect on ATase activity, but after 4 weeks ATase activity was increased by 40%. Following ethanol withdrawal, ATase activity remained elevated for at least 12 h, but, by 24 h, the activity had fallen to the uninduced control level. DNA glycosylase activities were again affected differently. After 1 week of dietary ethanol exposure, there was no effect on APNG activity but it was inhibited by 19% at 4 weeks. OXOG glycosylase activity, on the other hand, was increased by 53% after 1 week, but decreased by 40% after 4 weeks. Although some of these changes in DNA repair capacity were relatively small, over time, their potential impact on the repair of endogenous or exogenous alkylation and/or oxidation damage in DNA would be substantial. These studies indicate possible mechanisms for the co-carcinogenic effects of ethanol.


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