JaLCDOI 10.18926/AMO/48262
フルテキストURL 66_2_119.pdf.pdf
著者 Oka, Hiroaki| Ouchida, Mamoru| Kondo, Takuya| Morita, Fumio| Shimizu, Kenji|
抄録 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.
キーワード 5-fluorouracil TP53 Tk mutation assays microarray analysis
Amo Type Original Article
発行日 2012-04
出版物タイトル Acta Medica Okayama
出版者 Okayama University Medical School
開始ページ 119
終了ページ 129
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
著作権者 CopyrightⒸ 2012 by Okayama University Medical School
論文のバージョン publisher
査読 有り
PubMed ID 22525470
Web of Science KeyUT 000303175300005