Involvement of ribonucleotide reductase-M1 in 5-fluorouracil-induced DNA damage in esophageal cancer cell lines

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Involvement of ribonucleotide reductase-M1 in 5-fluorouracil-induced DNA damage in esophageal cancer cell lines

Material type: 博士論文

Author: Aoki, Yoshiro

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Material Format: Digital

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Name of awarding university/degree: 広島大学(Hiroshima University),博士(医学)

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Note (General)：: type:text5-Fluorouracil (5-FU) is one of the most well established chemotherapeutic agents in the treatment of esophageal cancer. Ribonucleotide reduc...

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Material Type: 博士論文
Title: Involvement of ribonucleotide reductase-M1 in 5-fluorouracil-induced DNA damage in esophageal cancer cell lines
Author/Editor: Aoki, Yoshiro
Author Heading: Aoki, Yoshiro
Alternative Title: 食道癌細胞株における5-フルオロウラシルにより誘導されるDNA障害へのリボヌクレオチドリダクターゼM1の関与
Degree grantor/type: 広島大学(Hiroshima University)
Date Granted: 2013-05-23
Dissertation Number: 甲第6190号
Degree Type: 博士(医学)
Text Language Code: eng
Subject Heading: ribonucleotide reductase
cisplatin
5-fluorouracil
γ-H2AX
RAD51
NDC: 490
Target Audience: 一般
Note (General): type:text
5-Fluorouracil (5-FU) is one of the most well established chemotherapeutic agents in the treatment of esophageal cancer. Ribonucleotide reductase M1 (RRM-1) is the rate?limiting enzyme in de novo DNA synthesis, and has been considered to play an important role in the 5-FU metabolic pathway. However, the means by which RRM-1 participates in the anticancer effects of 5-FU and cisplatin (CDDP) have not been well studied. Here, we show that RRM-1 significantly contributes to the induction of DNA damage by 5-FU in esophageal cancer cell lines. An assay of γ-H2AX focus forma-tion, a marker of DNA damage, after 5-FU treatment revealed good correlation with the levels of RRM-1 protein expression. Moreover, the increased sensitivity and RAD51 focus forma-tion induced by the combination treatment of 5-FU and CDDP were significantly repressed by RRM-1 depletion. These results suggest that RRM-1 is involved not only in the induction of DNA damage by 5-FU but also in the synergistic cytotoxic effect in the combination therapy of 5-FU and CDDP.
Format (IMT): application/pdf
Source: fulltext
http://ir.lib.hiroshima-u.ac.jp/files/public/3/36258/20141121004700420800/k6190_3.pdf
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http://ir.lib.hiroshima-u.ac.jp/files/public/3/36258/20181116103750286991/k6190_1.pdf
fulltext
http://ir.lib.hiroshima-u.ac.jp/files/public/3/36258/20181116103750974193/k6190_2.pdf
Access Restrictions: インターネット公開
Rights (production): Copyright(c) by Author
References (URI): URI
http://dx.doi.org/10.3892/ijo.2013.1899
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 広島大学 : 広島大学学術情報リポジトリ