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Loss of P53 heterozygosity is not responsible for the small colony thymidine kinase mutant phenotype in L5178Y mouse lymphoma cells.

Authors
Clark-LS; Harrington-Brock-K; Wang-J; Sargent-L; Lowry-D; Reynolds-SH; Moore-MM
Source
Mutagenesis 2004 Jul; 19(4):263-268
NIOSHTIC No.
20025741
Abstract
The mouse lymphoma L5178Y Tk+/- 3.7.2C assay is a well-characterized in vitro system used for the study of somatic cell mutation. It was determined that this cell line has a heterozygous mutation in exon 5 of Trp53. Based on this assumption that the cell line is heterozygous for the Trp53 gene, it was postulated that the small colony thymidine kinase (Tk) mutant phenotype may be due to a newly induced mutation/deletion in both the Trp53 and Tk1 alleles. The resultant Tk-/- mutants would also be Trp53+/0 or Trp53+/+ and would lose their ability to grow at normal rates. Subsequently, we published our evaluation of the Trp53 status in L5178Y cells. This analysis included sequencing of Trp53 exon 4 and determined that the mouse lymphoma cell line has a mutation in both of the Trp53 alleles and, therefore, no wild-type Trp53 allele in either Tk+/- cells or Tk-/- mutants. Because the cells have no wild-type Trp53, it is not possible that the small colony phenotype results from a newly induced loss of both functional Trp53 and Tk. To determine whether small colonies might, however, include the deletion of both Trp53 and Tk we evaluated, using microsatellite marker analysis, a series of small colony mutants. We also utilized in situ hybridization to determine that the Trp53 alleles are, in fact, in their normal chromosome 11 location in Tk+/- 3.7.2C mouse lymphoma cells. From all of these analyses we can conclude that the small colony mutant phenotype is not caused by deletion of both Trp53 and Tk1.
Keywords
Laboratory-animals; Animals; Animal-studies; Mutation; Mutagenesis; Mutagenicity; In-vitro-studies; Cell-cultures
Contact
Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, HFT 120, 3900 NCTR Road, Jefferson, AR 72079, USA
CODEN
MUTAEX
Publication Date
20040701
Document Type
Journal Article
Email Address
mmmoore@nctr.fda.gov
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
4
ISSN
0267-8357
NIOSH Division
HELD
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
Mutagenesis
State
WV; NC; AR
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