title: γ-H2AX responds to DNA damage induced by long-term exposure to combined low-dose-rate neutron and γ-ray radiation.
abstract: Risk estimates for low-dose radiation (LDR) remain controversial. The possible involvement of DNA repair-related genes in long-term low-dose-rate neutron-gamma radiation exposure is poorly understood. In this study, 60 rats were divided into control groups and irradiated groups, which were exposed to low-dose-rate n-γ combined radiation (LDCR) for 15, 30, or 60 days. The effects of different cumulative radiation doses on peripheral blood cell (PBC), subsets of T cells of peripheral blood lymphocytes (PBL) and DNA damage repair were investigated. Real-time PCR and immunoblot analyses were used to detect expression of DNA DSB-repair-related genes involved in the NHEJ pathway, such as Ku70 and Ku80, in PBL. The mRNA level of H2AX and the expression level of γ-H2AX were detected by real-time PCR, immunoblot, and flow cytometry. White blood cells (WBC) and platelets (PLT) of all ionizing radiation (IR) groups decreased significantly, while no difference was seen between the 30 day and 60 day exposure groups. The numbers of CD3(+), CD4(+) T cells and CD4(+)/CD8(+) in the PBL of IR groups were lower than in the control group. In the 30 day and 60 day exposure groups, CD8(+) T cells decreased significantly. Real-time PCR and immunoblot results showed no significant difference in the mRNA and protein expression of Ku70 and Ku80 between the control groups and IR groups. However, the mRNA of H2AX increased significantly, and there was a positive correlation with dose. There was no difference in the protein expression of γ-H2AX between 30 day and 60 day groups, which may help to explain the damage to PBL. In conclusion, PBL damage increased with cumulative dose, suggesting that γ-H2AX, but neither Ku70 nor Ku80, plays an important role in PBL impairment induced by LDCR.
authors.affiliation: College of Food Science and Engineering, Shanghai Ocean University, Shanghai 201306, China; PLA Key Laboratory of Biological Effect and Medical Protection on Warship Special Environment, Department of Protection Medicine, Naval Medical Research Institute, Shanghai 200433, China.
authors.forename: Junlin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: PLA Key Laboratory of Biological Effect and Medical Protection on Warship Special Environment, Department of Protection Medicine, Naval Medical Research Institute, Shanghai 200433, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: PLA Key Laboratory of Biological Effect and Medical Protection on Warship Special Environment, Department of Protection Medicine, Naval Medical Research Institute, Shanghai 200433, China. Electronic address: xianrong_sh@163.com.
authors.forename: Xianrong
authors.initials: X
authors.lastname: Shen
authors.affiliation: PLA Key Laboratory of Biological Effect and Medical Protection on Warship Special Environment, Department of Protection Medicine, Naval Medical Research Institute, Shanghai 200433, China.
authors.forename: Dingwen
authors.initials: D
authors.lastname: Jiang
authors.affiliation: PLA Key Laboratory of Biological Effect and Medical Protection on Warship Special Environment, Department of Protection Medicine, Naval Medical Research Institute, Shanghai 200433, China.
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: PLA Key Laboratory of Biological Effect and Medical Protection on Warship Special Environment, Department of Protection Medicine, Naval Medical Research Institute, Shanghai 200433, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Biological Engineering, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Fang
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects*; D059766:DNA End-Joining Repair / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D000072200:Ku Autoantigen; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D006657:Histones; D010750:Phosphoproteins; D012333:RNA, Messenger; C577575:gamma-H2AX protein, rat; C000606511:Xrcc6 protein, rat; D000072200:Ku Autoantigen
keywords: (60)Co γ-ray; Ku70; Ku80; Low-dose radiation; Neutron; γ-H2AX