DNA repair deficient chinese hamster ovary cells exhibiting differential sensitivity to charged particle radiation under aerobic and hypoxic conditions

Ian M. Cartwright, Cathy Su, Jeremy S. Haskins, Victoria A. Salinas, Shigeaki Sunada, Hao Yu, Mitsuru Uesaka, Hirokazu Hirakawa, David J. Chen, Akira Fujimori, Takamitsu A. Kato

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

It has been well established that hypoxia significantly increases both cellular and tumor resistance to ionizing radiation. Hypoxia associated radiation resistance has been known for some time but there has been limited success in sensitizing cells to radiation under hypoxic conditions. These studies show that, when irradiated with low linear energy transfer (LET) gamma-rays, poly (ADP-ribose), polymerase (PARP), Fanconi Anemia (FANC), and mutant Chinese Hamster Ovary (CHO) cells respond similarly to the non-homologous end joining (NHEJ) and the homologous recombination (HR) repair mutant CHO cells. Comparable results were observed in cells exposed to 13 keV/µm carbon ions. However, when irradiated with higher LET spread out Bragg peak (SOBP) carbon ions, we observed a decrease in the oxygen enhancement ratio (OER) in all the DNA of repair mutant cell lines. Interestingly, PARP mutant cells were observed as having the largest decrease in OER. Finally, these studies show a significant increase in the relative biological effectiveness (RBE) of high LET SOBP carbon and iron ions in HR and PARP mutants. There was also an increase in the RBE of NHEJ mutants when irradiated to SOBP carbon and iron ions. However, this increase was lower than in other mutant cell lines. These findings indicate that high LET radiation produces unique types of DNA damage under hypoxic conditions and PARP and HR repair pathways play a role in repairing this damage.

Original languageEnglish (US)
Article number2228
JournalInternational journal of molecular sciences
Volume19
Issue number8
DOIs
StatePublished - Aug 2018

Keywords

  • DNA repair
  • Ionizing radiation
  • LET
  • OER
  • RBE

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Cartwright, I. M., Su, C., Haskins, J. S., Salinas, V. A., Sunada, S., Yu, H., Uesaka, M., Hirakawa, H., Chen, D. J., Fujimori, A., & Kato, T. A. (2018). DNA repair deficient chinese hamster ovary cells exhibiting differential sensitivity to charged particle radiation under aerobic and hypoxic conditions. International journal of molecular sciences, 19(8), [2228]. https://doi.org/10.3390/ijms19082228