title: Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells.
abstract: OBJECTIVE
  To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons.
  
  
  METHODS
  The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions.
  
  
  RESULTS
  The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons (P<.05 for both cells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams (P<.05).
  
  
  CONCLUSIONS
  The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons.
authors.affiliation: Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya City West Medical Center, Nagoya, Japan; Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Electronic address: h-iwa-ncu@nifty.com.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya City West Medical Center, Nagoya, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ogino
authors.affiliation: Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya City West Medical Center, Nagoya, Japan; Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Radiation Oncology, Nagoya City West Medical Center, Nagoya, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Proton Therapy Technology, Nagoya Proton Therapy Center, Nagoya, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shibata
authors.affiliation: Department of Proton Therapy Technology, Nagoya Proton Therapy Center, Nagoya, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yasui
authors.affiliation: Department of Proton Therapy Physics, Nagoya Proton Therapy Center, Nagoya, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Toshito
authors.affiliation: Department of Proton Therapy Physics, Nagoya Proton Therapy Center, Nagoya, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Omachi
authors.affiliation: Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kotoha
authors.initials: K
authors.lastname: Tatekawa
authors.affiliation: Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Manabe
authors.affiliation: Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya City West Medical Center, Nagoya, Japan.
authors.forename: Jun-Etsu
authors.initials: JE
authors.lastname: Mizoe
authors.affiliation: Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Shibamoto
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D018499:Linear Energy Transfer; D051379:Mice; D010100:Oxygen / Q000378:metabolism / Q000528:radiation effects*; D017785:Photons; D061766:Proton Therapy; D011522:Protons; D011837:Radiation-Protective Agents / Q000494:pharmacology; D012062:Relative Biological Effectiveness; D012542:Scattering, Radiation; D013440:Sulfides / Q000494:pharmacology; D014965:X-Rays
chemical_list: D011522:Protons; D011837:Radiation-Protective Agents; D013440:Sulfides; C004784:dimethyl sulfide; D010100:Oxygen