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Open AccessArticle

DNA Repair Deficient Chinese Hamster Ovary Cells Exhibiting Differential Sensitivity to Charged Particle Radiation under Aerobic and Hypoxic Conditions

1
Department of Environmental & Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA
2
Mucosal Inflammation Program and Division of Gastroenterology, University of Colorado, Anshutz Medical Campus, Aurora, CO 80045, USA
3
School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan
4
Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
5
Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Chiba 263-8555, Japan
6
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(8), 2228; https://doi.org/10.3390/ijms19082228
Received: 8 May 2018 / Revised: 18 July 2018 / Accepted: 23 July 2018 / Published: 30 July 2018
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research)
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. View Full-Text
Keywords: ionizing radiation; DNA repair; LET; OER; RBE ionizing radiation; DNA repair; LET; OER; RBE
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MDPI and ACS Style

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. DNA Repair Deficient Chinese Hamster Ovary Cells Exhibiting Differential Sensitivity to Charged Particle Radiation under Aerobic and Hypoxic Conditions. Int. J. Mol. Sci. 2018, 19, 2228. https://doi.org/10.3390/ijms19082228

AMA Style

Cartwright IM, Su C, Haskins JS, Salinas VA, Sunada S, Yu H, Uesaka M, Hirakawa H, Chen DJ, Fujimori A, Kato TA. DNA Repair Deficient Chinese Hamster Ovary Cells Exhibiting Differential Sensitivity to Charged Particle Radiation under Aerobic and Hypoxic Conditions. International Journal of Molecular Sciences. 2018; 19(8):2228. https://doi.org/10.3390/ijms19082228

Chicago/Turabian Style

Cartwright, Ian M.; Su, Cathy; Haskins, Jeremy S.; Salinas, Victoria A.; Sunada, Shigeaki; Yu, Hao; Uesaka, Mitsuru; Hirakawa, Hirokazu; Chen, David J.; Fujimori, Akira; Kato, Takamitsu A. 2018. "DNA Repair Deficient Chinese Hamster Ovary Cells Exhibiting Differential Sensitivity to Charged Particle Radiation under Aerobic and Hypoxic Conditions" Int. J. Mol. Sci. 19, no. 8: 2228. https://doi.org/10.3390/ijms19082228

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