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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1996-6-21
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pubmed:abstractText |
Urethane (ethyl carbamate) is a genotoxic carcinogen that requires metabolic activation. Ethanol is known to inhibit urethane metabolism and genotoxicity. Since ethanol is eliminated rapidly in animals, the persistence of ethanol inhibition was studied in a mouse bone marrow and a peripheral blood micronucleus assays. In the bone marrow assay, male CD-1 mice were injected intraperitoneally (i.p.) with water (vehicle), urethane (1000 mg/kg), ethanol (2500 mg/kg) or urethane and ethanol (1000 and 2500 mg/kg, respectively) in single injections. Polychromatic erythrocytes (PCE) from bone marrow were obtained at 24 and 48 h after injection and scored for micronuclei. Urethane induced an increase of micronucleated PCE (MN PCE) frequency from 0.19% in the control to 8.63% at 24 h, followed by a decrease to 6.98% at 48 h. When urethane was co-administered with ethanol, the MN PCE frequency was suppressed to 0.49% at 24 h, but markedly increased to 7.35% at 48 h. This delay of MN PCE occurrence indicated that ethanol inhibition was transient. To pinpoint the duration of this delay, a peripheral blood micronucleus assay was conducted to monitor the kinetics of MN PCE induction. In this assay, male CD-1 mice were injected i.p. with water, ethanol, urethane, or urethane and ethanol as described above. Peripheral blood was scored for MN PCE at 8-h intervals for 4 days. Two additional dose groups injected with urethane or urethane and ethanol were also scored for MN PCE at 8 h intervals, but each blood sampling time was staggered 4 h later from the first four dose groups. The combined data provided MN PCE frequencies at 4-h intervals from 24 to 100 h after injection. Urethane alone induced a peak MN PCE frequency of 11.6% at 52 h. Urethane and ethanol induced a peak MN PCE frequency of 11.2% at 64 h, a delay of 12 h. Thus, ethanol delays but does not diminish urethane genotoxicity.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0027-5107
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
367
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
237-44
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:8628331-Animals,
pubmed-meshheading:8628331-Bone Marrow,
pubmed-meshheading:8628331-Carcinogens,
pubmed-meshheading:8628331-Drug Interactions,
pubmed-meshheading:8628331-Erythrocytes,
pubmed-meshheading:8628331-Ethanol,
pubmed-meshheading:8628331-Kinetics,
pubmed-meshheading:8628331-Male,
pubmed-meshheading:8628331-Mice,
pubmed-meshheading:8628331-Mice, Inbred Strains,
pubmed-meshheading:8628331-Micronuclei, Chromosome-Defective,
pubmed-meshheading:8628331-Micronucleus Tests,
pubmed-meshheading:8628331-Mutagens,
pubmed-meshheading:8628331-Urethane
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pubmed:year |
1996
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pubmed:articleTitle |
Co-administration of ethanol transiently inhibits urethane genotoxicity as detected by a kinetic study of micronuclei induction in mice.
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pubmed:affiliation |
Safety Evaluation Center, Schering-Plough Research Institute, Lafayette, NJ 07848, USA.
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pubmed:publicationType |
Journal Article
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