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Oka, Hiroaki Tokushima Research Center, Taiho pharmaceutical Co., Ltd.
Ouchida, Mamoru Department of Molecular Genetics, Okayama University Graduate School of Medicine 科研費研究者番号
Kondo, Takuya Tokushima Research Center, Taiho pharmaceutical Co., Ltd.
Morita, Fumio Tokushima Research Center, Taiho pharmaceutical Co., Ltd.
Shimizu, Kenji Department of Molecular Genetics, Okayama University Graduate School of Medicine
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.
Tk mutation assays
Acta Medica Okayama
Okayama University Medical School
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