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Mutant frequency and mutational spectra in theTk andHprt genes ofN-ethyl-N-nitrosourea-treated mouse lymphoma cells
- Source :
- Environmental and Molecular Mutagenesis. 39:296-305
- Publication Year :
- 2002
- Publisher :
- Wiley, 2002.
-
Abstract
- The mouse lymphoma assay (MLA) utilizing the Tk gene is widely used to identify chemical mutagens. The autosomal location of the Tk gene allows for the detection of a wide range of mutational events, from point mutations to chromosome alterations. However, chemically induced point mutation spectra in the Tk gene of mouse lymphoma cells have not been characterized. In this study, we determined and compared the mutagenicity and mutational spectra of N-ethyl-N-nitrosourea (ENU) in the Tk and Hprt genes of mouse lymphoma cells. Treatment of L5178Y mouse lymphoma cells with 100 μg/ml ENU induced a Tk mutant frequency of 756 × 10−6 and an Hprt mutant frequency of 311 × 10−6. Sequence analysis of Tk and Hprt mutant cDNAs showed a similar overall mutation pattern in the two genes with base-pair substitutions accounting for 83% of non–loss of heterozygosity mutations in the Tk gene and 75% of all mutations in the Hprt gene. The most common point mutation induced by ENU was G:C A:T transition (36 and 28% of independent mutations detected in the Tk and Hprt genes, respectively). The mutation spectra induced by ENU in both the Tk and Hprt genes were different from the respective patterns produced in mutants from untreated cells. About 9% of Tk and 7% of Hprt mutations from control cells were in-frame deletions, whereas no such mutations were found among the ENU-induced Tk and Hprt mutations. Our results indicate that ENU produces a chemical-specific point mutational profile in the Tk gene of mouse lymphoma cells that is remarkably similar to that found in the X-linked Hprt gene. This study provides evidence that the MLA can be used not only to detect point mutagens but also for analysis of mutational spectra. Environ. Mol. Mutagen. 39:296–305, 2002. Published 2002 Wiley-Liss, Inc.
- Subjects :
- Hypoxanthine Phosphoribosyltransferase
Lymphoma
Epidemiology
Health, Toxicology and Mutagenesis
DNA Mutational Analysis
Mutant
Mutagen
Biology
medicine.disease_cause
Loss of heterozygosity
Mice
Tumor Cells, Cultured
medicine
Animals
Point Mutation
Gene
Genetics (clinical)
Genetics
Mutation
Mutation Spectra
Transition (genetics)
Mutagenicity Tests
Point mutation
Sequence Analysis, DNA
Protein-Tyrosine Kinases
Molecular biology
Ethylnitrosourea
Carcinogens
Subjects
Details
- ISSN :
- 10982280 and 08936692
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Environmental and Molecular Mutagenesis
- Accession number :
- edsair.doi.dedup.....12928ed7ff8c9bcdae11490495f258bb
- Full Text :
- https://doi.org/10.1002/em.10075