title: Differences in sustained alterations in protein expression between livers of mice exposed to high-dose-rate and low-dose-rate radiation.
abstract: Molecular mechanisms of radiation dose-rate effects are not well understood. Among many possibilities, long-lasting sustained alterations in protein levels would provide critical information. To evaluate sustained effects after acute and chronic radiation exposure, we analyzed alterations in protein expression in the livers of mice. Acute exposure consisted of a lethal dose of 8 Gy and a sublethal dose of 4 Gy, with analysis conducted 6 days and 3 months after irradiation, respectively. Chronic irradiation consisted of a total dose of 8 Gy delivered over 400 days (20 mGy/day). Analyses following chronic irradiation were done immediately and at 3 months after the end of the exposure. Based on antibody arrays of protein expression following both acute lethal and sublethal dose exposures, common alterations in the expression of two proteins were detected. In the sublethal dose exposure, the expression of additional proteins was altered 3 months after irradiation. Immunohistochemical analysis showed that the increase in one of the two commonly altered proteins, MyD88, was observed around blood vessels in the liver. The alterations in protein expression after chronic radiation exposure were different from those caused by acute radiation exposures. Alterations in the expression of proteins related to inflammation and apoptosis, such as caspase 12, were observed even at 3 months after the end of the chronic radiation exposure. The alterations in protein expression depended on the dose, the dose rate, and the passage of time after irradiation. These changes could be involved in long-term effects of radiation in the liver.
authors.affiliation: National Institute of Radiological Sciences, National Institutes of Quantum and Radiological Science and Technology, 9-1, Anagawa-4-chome, Inage-ku, Chiba-shi 263-8555, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: National Institute of Radiological Sciences, National Institutes of Quantum and Radiological Science and Technology, 9-1, Anagawa-4-chome, Inage-ku, Chiba-shi 263-8555, Japan.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Radiobiology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho-mura, Kamikita-gun, Aomori 039-3212, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ono
authors.affiliation: Department of Cell Biology, Tohoku University School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Uehara
authors.affiliation: Department of Radiobiology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho-mura, Kamikita-gun, Aomori 039-3212, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Radiobiology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho-mura, Kamikita-gun, Aomori 039-3212, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ichinohe
authors.affiliation: Department of Radiobiology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho-mura, Kamikita-gun, Aomori 039-3212, Japan.
authors.forename: Ignacia
authors.initials: I
authors.lastname: Braga-Tanaka
authors.affiliation: Department of Radiobiology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho-mura, Kamikita-gun, Aomori 039-3212, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Radiobiology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho-mura, Kamikita-gun, Aomori 039-3212, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: National Institute of Radiological Sciences, National Institutes of Quantum and Radiological Science and Technology, 9-1, Anagawa-4-chome, Inage-ku, Chiba-shi 263-8555, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nenoi
mesh_terms: D000818:Animals; D053454:Caspase 12 / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
chemical_list: D007797:Laminin; D053594:Myeloid Differentiation Factor 88; D011506:Proteins; D053454:Caspase 12
keywords: acute irradiation effects; antibody array; low-dose-rate irradiation effects; mouse liver; protein expression