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 Ouchida, Takuya Kondo, Fumio Morita, Kenji Shimizu

Research output: Contribution to journalArticlepeer-review

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
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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