Source:http://linkedlifedata.com/resource/pubmed/id/20035728
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-2
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pubmed:dateCreated |
2010-3-26
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pubmed:abstractText |
Hprt mutant frequency and p53 gene status were assessed in wild-type and p53 heterozygous (p53+/-) mice exposed chronically by inhalation to benzene. Benzene exposures to 100 ppm for 6h on Monday-Friday, 100 ppm for 10h on Monday-Wednesday-Friday, or 200 ppm for 5h on Monday-Wednesday-Friday yielded the same total exposures (concentration x time) of 3000 ppm x h/week. Hprt mutations in splenic T-lymphocytes were significantly increased in all benzene groups, ranging from 3.8- to 8.0-fold greater than control values. Wild-type and p53+/- mice were equally susceptible to benzene mutagenesis. Hprt wild-type and mutant isolates from control and exposed animals were examined for TCR gene rearrangements (as markers of in vivo clonality) and for loss of p53 wild-type or mutant alleles. Moderate clonal amplifications were observed among the Hprt mutant but not Hprt wild-type isolates but was not sufficient to account for the increases in Hprt mutant frequencies. Most isolates, whether Hprt wild-type or mutant, retained both p53 alleles in the benzene-exposed p53+/- animals (54% and 63%, respectively, for the Hprt wild-type and mutants). However, 37% of the Hprt wild-type isolates and 46% of the Hprt mutant isolates lost the p53 mutant allele. Only a small percentage of either type of isolate lost the p53 wild-type allele, and this was always in isolates that that previously lost the p53 mutant allele. Loss of the p53 mutant allele was independent of benzene exposure, Hprt status, or 6-thioguanine selection. These findings contrast with the p53 status of thymic lymphomas that had preferentially lost the wild-type p53 allele in some of these same mice. Possible reasons for loss of the mutant p53 allele in the Hprt mutant and wild-type isolates are discussed.
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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 |
Mar
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pubmed:issn |
1872-7786
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pubmed:author | |
pubmed:copyrightInfo |
Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
184
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
77-85
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pubmed:meshHeading |
pubmed-meshheading:20035728-Animals,
pubmed-meshheading:20035728-Benzene,
pubmed-meshheading:20035728-Genes, p53,
pubmed-meshheading:20035728-Hypoxanthine Phosphoribosyltransferase,
pubmed-meshheading:20035728-Inhalation Exposure,
pubmed-meshheading:20035728-Loss of Heterozygosity,
pubmed-meshheading:20035728-Lymphoma, T-Cell,
pubmed-meshheading:20035728-Mice,
pubmed-meshheading:20035728-Mice, Inbred C57BL,
pubmed-meshheading:20035728-Mutagens,
pubmed-meshheading:20035728-Mutation,
pubmed-meshheading:20035728-Receptors, Antigen, T-Cell,
pubmed-meshheading:20035728-T-Lymphocytes
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pubmed:year |
2010
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pubmed:articleTitle |
Hprt mutant frequency and p53 gene status in mice chronically exposed by inhalation to benzene.
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pubmed:affiliation |
Department of Pathology, University of Vermont, Burlington, VT 05404, USA. Ralbert315@aol.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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