ID | 48262 |
JaLCDOI | |
FullText URL | |
Author |
Oka, Hiroaki
Kondo, Takuya
Morita, Fumio
Shimizu, Kenji
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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.
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Keywords | 5-fluorouracil
TP53
Tk mutation assays
microarray analysis
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Amo Type | Original Article
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Publication Title |
Acta Medica Okayama
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Published Date | 2012-04
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Volume | volume66
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Issue | issue2
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Publisher | Okayama University Medical School
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Start Page | 119
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End Page | 129
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ISSN | 0386-300X
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NCID | AA00508441
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Content Type |
Journal Article
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language |
English
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Copyright Holders | CopyrightⒸ 2012 by Okayama University Medical School
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File Version | publisher
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Refereed |
True
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PubMed ID | |
Web of Science KeyUT |