Ethanol-induced free radicals and hepatic DNA strand breaks are prevented in vivo by antioxidants: effects of acute and chronic ethanol exposure.

2.50
Hdl Handle:
http://hdl.handle.net/10541/90073
Title:
Ethanol-induced free radicals and hepatic DNA strand breaks are prevented in vivo by antioxidants: effects of acute and chronic ethanol exposure.
Authors:
Navasumrit, Panidz; Ward, Timothy H; Dodd, Nicholas J F; O'Connor, Peter J
Abstract:
Ethanol was given to male Wistar rats as an acute dose (5 g/kg) or continuously at 5% (w/v) in a liquid diet to provide 36% of the caloric requirement. Free radicals generated in the liver were collected as a stable adduct in bile following the in vivo administration of the spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN; 700 mg/kg). [1-(13)C]ethanol was used to confirm the formation of the 1-hydroxyethyl radical and to demonstrate that this was ethanol-derived in the case of the single-dose treatment. Free radical production increased up to 1h after the acute dose and then plateaued over the next 30 min. During chronic exposure to ethanol, free radical generation increased significantly after 1 week and then declined again to remain at a low level over the next 2 weeks; this transient increase corresponded closely with the induction of cytochrome P-450 2E1 (CYP 2E1) in response to ethanol feeding. Single-cell electrophoresis was used to investigate effects on DNA. After an acute dose of ethanol, the frequency of single-strand breaks increased from 1 h to peak at 6 h but then declined again to control values by 12 h. During the chronic exposure, an increase in the frequency of DNA breaks was seen at 3 days, reached a peak at 1 week and then decreased slowly over the next 5 weeks. The effects of antioxidants on these parameters was investigated after an acute dose of ethanol. Pre-treatment with vitamin C (400 mg/kg, i.p., daily for 5 days) or vitamin E (100 mg/kg, i.p., for 5 days) prior to the administration of ethanol (5 g/kg) inhibited generation of the 1-hydroxyethyl-POBN adduct by 30 and 50%, respectively, and both agents prevented the increased frequency of DNA single-strand breaks caused by ethanol. The significance of the temporal coincidence of changes in the above parameters in response to ethanol is discussed.
Affiliation:
Cancer Research Campaign, Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester M20 4BX, UK.
Citation:
Ethanol-induced free radicals and hepatic DNA strand breaks are prevented in vivo by antioxidants: effects of acute and chronic ethanol exposure. 2000, 21 (1):93-9 Carcinogenesis
Journal:
Carcinogenesis
Issue Date:
Jan-2000
URI:
http://hdl.handle.net/10541/90073
DOI:
10.1093/carcin/21.1.93
PubMed ID:
10607739
Type:
Article
Language:
en
ISSN:
0143-3334
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorNavasumrit, Panidzen
dc.contributor.authorWard, Timothy Hen
dc.contributor.authorDodd, Nicholas J Fen
dc.contributor.authorO'Connor, Peter Jen
dc.date.accessioned2010-01-19T17:06:59Z-
dc.date.available2010-01-19T17:06:59Z-
dc.date.issued2000-01-
dc.identifier.citationEthanol-induced free radicals and hepatic DNA strand breaks are prevented in vivo by antioxidants: effects of acute and chronic ethanol exposure. 2000, 21 (1):93-9 Carcinogenesisen
dc.identifier.issn0143-3334-
dc.identifier.pmid10607739-
dc.identifier.doi10.1093/carcin/21.1.93-
dc.identifier.urihttp://hdl.handle.net/10541/90073-
dc.description.abstractEthanol was given to male Wistar rats as an acute dose (5 g/kg) or continuously at 5% (w/v) in a liquid diet to provide 36% of the caloric requirement. Free radicals generated in the liver were collected as a stable adduct in bile following the in vivo administration of the spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN; 700 mg/kg). [1-(13)C]ethanol was used to confirm the formation of the 1-hydroxyethyl radical and to demonstrate that this was ethanol-derived in the case of the single-dose treatment. Free radical production increased up to 1h after the acute dose and then plateaued over the next 30 min. During chronic exposure to ethanol, free radical generation increased significantly after 1 week and then declined again to remain at a low level over the next 2 weeks; this transient increase corresponded closely with the induction of cytochrome P-450 2E1 (CYP 2E1) in response to ethanol feeding. Single-cell electrophoresis was used to investigate effects on DNA. After an acute dose of ethanol, the frequency of single-strand breaks increased from 1 h to peak at 6 h but then declined again to control values by 12 h. During the chronic exposure, an increase in the frequency of DNA breaks was seen at 3 days, reached a peak at 1 week and then decreased slowly over the next 5 weeks. The effects of antioxidants on these parameters was investigated after an acute dose of ethanol. Pre-treatment with vitamin C (400 mg/kg, i.p., daily for 5 days) or vitamin E (100 mg/kg, i.p., for 5 days) prior to the administration of ethanol (5 g/kg) inhibited generation of the 1-hydroxyethyl-POBN adduct by 30 and 50%, respectively, and both agents prevented the increased frequency of DNA single-strand breaks caused by ethanol. The significance of the temporal coincidence of changes in the above parameters in response to ethanol is discussed.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshAntioxidants-
dc.subject.meshAscorbic Acid-
dc.subject.meshCytochrome P-450 CYP2E1-
dc.subject.meshDNA-
dc.subject.meshDNA Damage-
dc.subject.meshEthanol-
dc.subject.meshFree Radicals-
dc.subject.meshLiver-
dc.subject.meshMale-
dc.subject.meshNitrogen Oxides-
dc.subject.meshPyridines-
dc.subject.meshRats-
dc.subject.meshRats, Wistar-
dc.subject.meshVitamin E-
dc.titleEthanol-induced free radicals and hepatic DNA strand breaks are prevented in vivo by antioxidants: effects of acute and chronic ethanol exposure.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign, Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester M20 4BX, UK.en
dc.identifier.journalCarcinogenesisen
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