title: Generation of low-flux X-ray micro-planar beams and their biological effect on a murine subcutaneous tumor model.
abstract: We generated low-flux X-ray micro-planar beams (MPBs) using a laboratory-scale industrial X-ray generator (60 kV/20 mA) with custom-made collimators with three different peak/pitch widths (50/200 μm, 100/400 μm, 50/400 μm). To evaluate normal skin reactions, the thighs of C3H/HeN mice were exposed to 100 and 200 Gy MPBs in comparison with broad beams (20, 30, 40, 50, 60 Gy). Antitumor effects of MPBs were evaluated in C3H/HeN mice with subcutaneous tumors (SCCVII). After the tumors were irradiated with 100 and 200 Gy MPBs and 20 and 30 Gy broad beams, the tumor sizes were measured and survival analyses were performed. In addition, the tumors were excised and immunohistochemically examined to detect γ-H2AX, ki67 and CD34. It was shown that antitumor effects of 200 Gy MPBs at 50/200 μm and 100/400 μm were significantly greater than those of 20 Gy broad beams, and were comparable with 30 Gy broad beams. γ-H2AX-positive cells demonstrated clear stripe-patterns after MPB irradiation; the pattern gradually faded and intermixed over 24 h. The chronological changes in ki67 positivity did not differ between MPBs and broad beams, whereas the CD34-positive area decreased significantly more in MPBs than in broad beams. In addition, it was shown that skin injury after MPB irradiation was significantly milder when compared with broad-beam irradiation at equivalent doses for achieving the same tumor control effect. Bystander effect and tumor vessel injury may be the mechanism contributing to the efficacy of MPBs.
authors.affiliation: Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Zhengshan
authors.initials: Z
authors.lastname: Hong
authors.affiliation: Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Zenkoh
authors.affiliation: Ningbo M&J Biotechnologies Co. Ltd, 299 GuangHua Road, Building C6, Suite 1, High-tech Zone, Ningbo City, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Le
authors.affiliation: Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Ariungerel
authors.initials: A
authors.lastname: Gerelchuluun
authors.affiliation: Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kenshi
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Radiological Health Science, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Moritake
authors.affiliation: Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Washio
authors.affiliation: High Energy Accelerator Research Organization, 1-1 Oho, Tsukuba, Ibaraki 305-0801, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Urakawa
authors.affiliation: Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan tsuboi-k@md.tsukuba.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuboi
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D024201:Bystander Effect; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy; D003872:Dermatitis / Q000209:etiology; D004307:Dose-Response Relationship, Radiation; D004867:Equipment Design; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D011832:Radiation Injuries; D011874:Radiometry; D012825:Silicon / Q000737:chemistry; D012867:Skin / Q000528:radiation effects; D013997:Time Factors; D014965:X-Rays
chemical_list: D018952:Antigens, CD34; D019394:Ki-67 Antigen; D012825:Silicon
keywords: antitumor effects; bystander effect; micro-planar beams; skin reaction