title: A Nucleoside Anticancer Drug, 1-(3-C-Ethynyl-β-D-Ribo-Pentofuranosyl)Cytosine, Induces Depth-Dependent Enhancement of Tumor Cell Death in Spread-Out Bragg Peak (SOBP) of Proton Beam.
abstract: The effect of 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd) on proton-induced cell death was evaluated in human lung carcinoma cell line A549 and Chinese hamster fibroblast cell line V79 to enhance relative biological effectiveness (RBE) within the spread-out Bragg peak (SOBP) of proton beams. Treatment with ECyd significantly enhanced the proton-induced loss of clonogenicity and increased senescence at the center, but not at the distal edge of SOBP. The p53-binding protein 1 foci formation assay showed that ECyd decelerated the rate of DNA double-strand break (DSB) repair at the center, but not the distal region of SOBP, suggesting that the ECyd-induced enhancement of proton-induced cell death is partially associated with the inhibition of DSB repair. This study demonstrated that ECyd enhances proton-induced cell killing at all positions of SOBP, except for the distal region and minimizes the site-dependent differences in RBE within SOBP. Thus, ECyd is a unique radiosensitizer for proton therapy that may be useful because it levels the biological dose within SOBP, which improves tumor control and reduces the risk of adverse effects at the distal edge of SOBP.
authors.affiliation: Department of Radiation Medicine, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamamori
authors.affiliation: Division of Quantum Science and Engineering, Faculty of Engineering, Hokkaido University, Kita 13 Nishi 8, Kita-ku, Sapporo, Hokkaido, 060-8628, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Matsuura
authors.affiliation: Proton Beam Therapy Center, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.
authors.forename: Seishin
authors.initials: S
authors.lastname: Takao
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan.
authors.forename: Motofumi
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo, Hokkaido, 060-0812, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Inanami
authors.affiliation: Department of Radiation Medicine, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.|Global Institution for Collaborative Research and Education, Hokkaido University, Kita 14 Nishi 5, Sapporo, Hokkaido, 060-8648, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shirato
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death; D006224:Cricetinae; D003412:Cricetulus; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D061766:Proton Therapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D003596:Cytosine