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ID 36258
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title alternative
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
creator
Aoki, Yoshiro
subject
ribonucleotide reductase
cisplatin
5-fluorouracil
γ-H2AX
RAD51
NDC
Medical sciences
abstract
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.
date of created
2014-11-21
language
eng
nii type
Thesis or Dissertation
HU type
Doctoral Theses
DCMI type
text
format
application/pdf
text version
ETD
rights
Copyright(c) by Author
relation references
YOSHIRO AOKI, KENJI SAKOGAWA, JUN HIHARA, MANABU EMI, YOICHI HAMAI, KAZUTERU KONO, LIN SHI, JIYING SUN, HIROYUKI KITAO, TSUYOSHI IKURA, HIROYUKI NIIDA, MAKOTO NAKANISHI, MORIHITO OKADA and SATOSHI TASHIRO; Involvement of ribonucleotide reductase-M1 in 5-fluorouracil-induced DNA damage in esophageal cancer cell lines; INTERNATIONAL JOURNAL OF ONCOLOGY 42: 1951-1960, 2013 (DOI: 10.3892/ijo.2013.1899)
relation references URL
http://dx.doi.org/10.3892/ijo.2013.1899
grantid
甲第6190号
degreeGrantor
広島大学(Hiroshima University)
degreename Ja
博士(医学)
degreename En
Philosophy in Medical Science
degreelevel
doctoral
date of granted
2013-05-23
department
Graduate School of Biomedical Science