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ID 48262
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Author
Oka, Hiroaki
Kondo, Takuya
Morita, Fumio
Shimizu, Kenji
Abstract
Human lymphoblastoid TK6 and WTK-1 cells are widely used to detect mutagens in vitro. TK6 cells have wild-type TP53 alleles, while WTK-1 cells have one allele of mutated TP53. Both cells were treated with 5-fluorouracil (5-FU), and gene mutation assay and micronucleus assay were performed to clarify the differential response related to the TP53 gene status. The effects of 5-FU on gene expression were assessed by microarray and quantitative RT-PCR analyses. In WTK-1 cells, 5-FU increased the frequency of cells with micronucleus and mutation. In TK6 cells, frequency of cells with micronucleus was increased but the mutation frequency was not. The cytotoxicity induced by 5-FU was more prominent in TK6 cells than in WTK-1 cells. Analysis of gene expression showed that the genes involved in the TP53 pathway were up-regulated in TK6 cells but not in WTK-1 cells. The differential responses to 5-FU between these cell lines appeared to be due to the difference in the TP53 gene status, thus providing a molecular basis for the bioassays using these cell lines in the toxicology field. Our results indicate that the clinical efficacy of 5-FU chemotherapy may depend on the TP53 genotype.
Keywords
5-fluorouracil
TP53
Tk mutation assays
microarray analysis
Amo Type
Original Article
Published Date
2012-04
Publication Title
Acta Medica Okayama
Volume
volume66
Issue
issue2
Publisher
Okayama University Medical School
Start Page
119
End Page
129
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
Copyright Holders
CopyrightⒸ 2012 by Okayama University Medical School
File Version
publisher
Refereed
True
PubMed ID
Web of Science KeyUT