Source:http://linkedlifedata.com/resource/pubmed/id/11880538
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2002-3-6
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| pubmed:abstractText |
N-ethyl-N-nitrosourea (ENU) is a potent monofunctional ethylating agent that has been found to be mutagenic in a wide variety of organisms from viruses to mammalian germ cells. To elucidate the mutagenicity of ENU at the Tk(+/-) locus of mouse lymphoma cells and to confirm the ability of the mouse lymphoma assay (MLA) to detect both point mutations and large DNA alterations, Tk(+/-) L5178Y cells were exposed to different doses of ENU. Treatment of the cells with ENU resulted in a linear dose response with mutant frequencies of up to 16-fold over control. Evaluation of mutant clone size showed that 36% of the 100 microg/ml ENU-induced clones (66% in control) were small colony mutants and 64% (34% in control) were large colony mutants. DNA isolated from mutants in the control culture and the 100 microg/ml ENU treatment group was analyzed for loss of heterozygosity (LOH) using allele-specific PCR. The majority of the small colony mutants, both ENU-treated (97%) and spontaneous (91%), lost the Tk1b allele. The percentage of allele loss in ENU-induced large colony mutants was distinctly different from that of the control. Twenty-three percent of ENU-induced large colony mutants lost their Tk1b alleles, whereas 73% of the large colony mutants from the control culture lost the allele (P < 0.001). Overall, 50% of the Tk mutants from the 100 microg/ml ENU-treated cultures (86% in control) showed LOH. Our data indicate that ENU is a potent mutagen in mouse lymphoma cells and that 100 microg/ml ENU induces equal numbers of point mutations and chromosomal mutations. This study serves to verify that the MLA detects both point mutations and chromosomal mutations.
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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 |
0267-8357
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
17
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
105-9
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11880538-Alkylating Agents,
pubmed-meshheading:11880538-Animals,
pubmed-meshheading:11880538-Base Sequence,
pubmed-meshheading:11880538-DNA Mutational Analysis,
pubmed-meshheading:11880538-Ethylnitrosourea,
pubmed-meshheading:11880538-Heterozygote,
pubmed-meshheading:11880538-Leukemia L5178,
pubmed-meshheading:11880538-Loss of Heterozygosity,
pubmed-meshheading:11880538-Mice,
pubmed-meshheading:11880538-Mice, Knockout,
pubmed-meshheading:11880538-Microsatellite Repeats,
pubmed-meshheading:11880538-Molecular Sequence Data,
pubmed-meshheading:11880538-Mutagenesis,
pubmed-meshheading:11880538-Mutagenicity Tests,
pubmed-meshheading:11880538-Point Mutation,
pubmed-meshheading:11880538-Sequence Analysis, DNA,
pubmed-meshheading:11880538-Sequence Homology, Nucleic Acid,
pubmed-meshheading:11880538-Thymidine Kinase,
pubmed-meshheading:11880538-Tumor Cells, Cultured
|
| pubmed:year |
2002
|
| pubmed:articleTitle |
Mutant frequencies and loss of heterozygosity induced by N-ethyl-N-nitrosourea in the thymidine kinase gene of L5178Y/TK(+/-)-3.7.2C mouse lymphoma cells.
|
| pubmed:affiliation |
Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA. tchen@nctr.fda.gov
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|