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Article

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

  • Authors:
    • 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
    • Satoshi Tashiro
  • View Affiliations / Copyright

    Affiliations: Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Minami-ku, Hiroshima, Japan, Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Minami-ku, Hiroshima, Japan, Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan, Department of Mutagenesis, Radiation Biology Center, Kyoto University, Sakyo-ku, Kyoto, Japan, Department of Molecular Biology, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan, Department of Experimental Pathology and Tumor Biology, Graduate School of Medical Sciences, Nagoya City University, Mizuho-ku, Nagoya, Japan
  • Pages: 1951-1960
    |
    Published online on: April 16, 2013
       https://doi.org/10.3892/ijo.2013.1899
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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 formation, 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 formation 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.
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Copy and paste a formatted citation
Spandidos Publications style
Aoki Y, Sakogawa K, Hihara J, Emi M, Hamai Y, Kono K, Shi L, Sun J, Kitao H, Ikura T, Ikura T, et al: Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines. Int J Oncol 42: 1951-1960, 2013.
APA
Aoki, Y., Sakogawa, K., Hihara, J., Emi, M., Hamai, Y., Kono, K. ... Tashiro, S. (2013). Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines. International Journal of Oncology, 42, 1951-1960. https://doi.org/10.3892/ijo.2013.1899
MLA
Aoki, Y., Sakogawa, K., Hihara, J., Emi, M., Hamai, Y., Kono, K., Shi, L., Sun, J., Kitao, H., Ikura, T., Niida, H., Nakanishi, M., Okada, M., Tashiro, S."Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines". International Journal of Oncology 42.6 (2013): 1951-1960.
Chicago
Aoki, Y., Sakogawa, K., Hihara, J., Emi, M., Hamai, Y., Kono, K., Shi, L., Sun, J., Kitao, H., Ikura, T., Niida, H., Nakanishi, M., Okada, M., Tashiro, S."Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines". International Journal of Oncology 42, no. 6 (2013): 1951-1960. https://doi.org/10.3892/ijo.2013.1899
Copy and paste a formatted citation
x
Spandidos Publications style
Aoki Y, Sakogawa K, Hihara J, Emi M, Hamai Y, Kono K, Shi L, Sun J, Kitao H, Ikura T, Ikura T, et al: Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines. Int J Oncol 42: 1951-1960, 2013.
APA
Aoki, Y., Sakogawa, K., Hihara, J., Emi, M., Hamai, Y., Kono, K. ... Tashiro, S. (2013). Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines. International Journal of Oncology, 42, 1951-1960. https://doi.org/10.3892/ijo.2013.1899
MLA
Aoki, Y., Sakogawa, K., Hihara, J., Emi, M., Hamai, Y., Kono, K., Shi, L., Sun, J., Kitao, H., Ikura, T., Niida, H., Nakanishi, M., Okada, M., Tashiro, S."Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines". International Journal of Oncology 42.6 (2013): 1951-1960.
Chicago
Aoki, Y., Sakogawa, K., Hihara, J., Emi, M., Hamai, Y., Kono, K., Shi, L., Sun, J., Kitao, H., Ikura, T., Niida, H., Nakanishi, M., Okada, M., Tashiro, S."Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines". International Journal of Oncology 42, no. 6 (2013): 1951-1960. https://doi.org/10.3892/ijo.2013.1899
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