Investigation of the relative biological effectiveness and uniform isobiological killing effects of irradiation with a clinical carbon SOBP beam on DNA repair deficient CHO cells

  • Authors:
    • Shigeaki Sunada
    • Ian M. Cartwright
    • Hirokazu Hirakawa
    • Akira Fujimori
    • Mitsuru Uesaka
    • Takamitsu A. Kato
  • View Affiliations

  • Published online on: April 21, 2017     https://doi.org/10.3892/ol.2017.6072
  • Pages: 4911-4916
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Abstract

Spread-out Bragg peak (SOBP) C ions have been used clinically in charged particle radiation therapy for years. An SOBP beam consists of various monoenergetic Bragg peaks; however, the biological effect of irradiation with an SOBP beam track has not been well‑studied. In order to determine the clinically prospective molecular targets, radiosensitivity to the beam track in DNA repair deficient cell lines was investigated. A total of four distinct Chinese hamster ovary (CHO) cell lines, including CHO10B2 (wild‑type), V3 (protein kinase DNA‑activated catalytic polypeptide deficient), 51D1 (RAD51 paralog D deficient) and PADR9 [poly(ADP‑ribose) polymerase (PARP) deficient], were irradiated with gamma‑rays, C ions (290 MeV/n) and Fe ions (500 MeV/n), in order to compare cellular lethality. An OptiCell™ culture system was used to evaluate the lethality at distinct depths of SOBP C ions. Relative biological effectiveness (RBE) values of C ions (linear energy transfer (LET), 13 and 70 keV/µm) and Fe ions (LET, 200 keV/µm) were calculated from cell survival using colony formation assay with standard cell dishes. All cell lines exhibited similar sensitivity to 70 keV/µm C ions and 200 keV/µm Fe ions. Furthermore, V3 cells did not exhibit increased sensitivity to high LET C ions and Fe ions, compared with low LET gamma‑rays and C ions, and 51D1 cells irradiated with 13 keV/µm C ions exhibited relatively high RBE values among the tested cell lines. Conversely, PADR9 cells exhibited low RBE values for 13 keV/µm C ions and high RBE values for 70 keV/µm C ions. Obtained using the OptiCell system, the survival fractions in the SOBP region were uniform for wild‑type and PADR9 cells. Conversely, V3 and 51D1 cells exhibited decreased cell death in the distal region of the SOBP. These results indicated that PARP is a more effective target for clinical beam therapy, compared with the non‑homologous end joining repair and homologous recombination repair pathways. PARP deficiency may be an optimal target for C ion therapy and the results of the present study may contribute to the development of a more effective heavy ion radiation therapy.
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June-2017
Volume 13 Issue 6

Print ISSN: 1792-1074
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Spandidos Publications style
Sunada S, Cartwright IM, Hirakawa H, Fujimori A, Uesaka M and Kato TA: Investigation of the relative biological effectiveness and uniform isobiological killing effects of irradiation with a clinical carbon SOBP beam on DNA repair deficient CHO cells. Oncol Lett 13: 4911-4916, 2017
APA
Sunada, S., Cartwright, I.M., Hirakawa, H., Fujimori, A., Uesaka, M., & Kato, T.A. (2017). Investigation of the relative biological effectiveness and uniform isobiological killing effects of irradiation with a clinical carbon SOBP beam on DNA repair deficient CHO cells. Oncology Letters, 13, 4911-4916. https://doi.org/10.3892/ol.2017.6072
MLA
Sunada, S., Cartwright, I. M., Hirakawa, H., Fujimori, A., Uesaka, M., Kato, T. A."Investigation of the relative biological effectiveness and uniform isobiological killing effects of irradiation with a clinical carbon SOBP beam on DNA repair deficient CHO cells". Oncology Letters 13.6 (2017): 4911-4916.
Chicago
Sunada, S., Cartwright, I. M., Hirakawa, H., Fujimori, A., Uesaka, M., Kato, T. A."Investigation of the relative biological effectiveness and uniform isobiological killing effects of irradiation with a clinical carbon SOBP beam on DNA repair deficient CHO cells". Oncology Letters 13, no. 6 (2017): 4911-4916. https://doi.org/10.3892/ol.2017.6072