Different responses to 5-f luoraouracil in mutagenicity and gene expression between two human lymphoblastoid cell lines with or without TP53 mutation

Hiroaki Oka, Mamoru Oouchida, Takuya Kondo, Fumio Morita, Kenji Shimizu

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)119-129
Number of pages11
JournalActa Medica Okayama
Volume66
Issue number2
Publication statusPublished - 2012

Fingerprint

Gene expression
Fluorouracil
Cells
Gene Expression
Cell Line
Mutation
Genes
Assays
Chemotherapy
Bioassay
p53 Genes
Mutagens
Cytotoxicity
Microarrays
Alleles
Micronucleus Tests
Mutation Rate
Biological Assay
Toxicology
Genotype

Keywords

  • 5-fluorouracil
  • Microarray analysis
  • Tk mutation assays
  • TP53

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Different responses to 5-f luoraouracil in mutagenicity and gene expression between two human lymphoblastoid cell lines with or without TP53 mutation. / Oka, Hiroaki; Oouchida, Mamoru; Kondo, Takuya; Morita, Fumio; Shimizu, Kenji.

In: Acta Medica Okayama, Vol. 66, No. 2, 2012, p. 119-129.

Research output: Contribution to journalArticle

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