title: Hyperthermia-induced radiosensitization in CHO wild-type, NHEJ repair mutant and HR repair mutant following proton and carbon-ion exposure.
abstract: The DNA repair mechanisms involved in hyperthermia-induced radiosensitization with proton and carbon ion radiation exposure were investigated in the present study. In a previous study, Chinese hamster ovary (CHO) cells were exposed to low linear energy transfer (LET) photon radiation. These cells can be sensitized by hyperthermia as a result of inhibition of homologous recombination (HR) repair. The present study used wild-type, non-homologous end joining (NHEJ) and HR repair-deficient CHO cells to define the contributions of each repair pathway to cellular lethality following hyperthermia-induced hadron radiation sensitization. The cells were exposed to ionizing radiation, followed by hyperthermia treatment (42.5°C for 1 h). Hyperthermia-induced radiosensitization was determined by the colony formation assay and thermal enhancement ratio. HR repair-deficient cells exhibited no hyper-sensitization to X-rays, protons, or low and high LET carbon ions when combined with hyperthermia. Wild-type and NHEJ repair-deficient cells exhibited significant hyperthermia-induced sensitization to low LET photon and hadron radiation. Hyperthermia-induced sensitization to high LET carbon-ion radiation was less than at low LET radiation. Relative biological effectiveness (RBE) between radiation alone and radiation combined with hyperthermia cell groups was not significantly different in any of the cell lines, with the exception of wild-type cells exposed to high LET radiation, which exhibited a lower RBE in the combined group. The present study investigated additional cell lines to confirm the lower RBE observed in DNA repair-deficient cell lines. These findings suggested that hyperthermia-induced hyper-sensitization to hadron radiation is also dependent on inhibition of HR repair, as was observed with photon radiation in a previous study.
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Junko
authors.initials: J
authors.lastname: Maeda
authors.affiliation: Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Inashiki, Ibaraki 300-0394, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujisawa
authors.affiliation: Research Center for Charged Particle Therapy, International Open Laboratory, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirakawa
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Cartwright
authors.affiliation: School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Uesaka
authors.affiliation: Research Development and Support Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kitamura
authors.affiliation: Research Center for Charged Particle Therapy, International Open Laboratory, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fujimori
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Takamitsu A
authors.initials: TA
authors.lastname: Kato
keywords: DNA repair; hadron radiation; hyperthermia