Project/Area Number |
06454327
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
Radiation science
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Research Institution | NATIONAL INSTITUTE OF RADIOLOGICAL SCIENCES |
Principal Investigator |
ANDO Koichi NATL INST RDIOL of SCI,THIRD RESEARCH GROUP,HEAD, 第3研究グループ, サブグループリーダー (00159526)
|
Co-Investigator(Kenkyū-buntansha) |
岩川 真由美 (岩川 眞由美) 筑波大学臨床医学系, 講師 (00159526)
NAKANO Takashi NATL INST RDIOL of SCI,DIV.RADIAT.MED,SUPERVIS.PHYSICIAN, 治療・診断部, 医長 (20211427)
OHYAMA Harumi NATL INST RDIOL of SCI,DIV.RAD.BIOL.BIODOS., HEALTH,HEAD, 障害基盤研究部, 室長 (70160645)
AKASHI Makoto NATL INST RDIOL of SCI,DIV.CL RES.RAD.HEALTH.HEAD, 障害・臨床研究部, 室長 (10222514)
|
Project Period (FY) |
1994 – 1995
|
Project Status |
Completed (Fiscal Year 1995)
|
Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1995: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1994: ¥3,100,000 (Direct Cost: ¥3,100,000)
|
Keywords | superoxides / DNA double strand breaks / p53 / WAF1 / heavy charged particles / RBE / Ly-^e antigen / uterine cervix / 子宮頸癌 / Le^y抗原 / 転移 / エンドヌクレアーゼ / G1期 / 重粒子線 / MnSOD |
Research Abstract |
What we found and disclosed on radiation-induced apoptosis were as follows : (1)X ray radiation to rats increased intracellular superoxides along with apoptosis in thymes.As the increase was not observed shortly after irradiation and, as similar increase of superoxides is also observed after glucocorticoid treatment, it is likely that the superoxides are produced not by radiation chemical reaction. (2)L5178Y-S leukemic cells are deficient of repairing DNA double strand breaks.X ray radiation arrested L5178Y-S cells at G2/M and induced apoptosis before cells entering into G1 phase.As parental cell line of L5178Y rather showed post-mitotic apoptosis after a large doses of radiation, capacity of cells to repair DNA double strand breaks could be related to timing of apoptosis. (3)A myeloid leukemia of human KG1 cells can not express p53 due to an insertion of extra 5 bases.X radiation to KG1 cells induced induced tumor necrosis factor and WAF1 as well.The WAF1 induction was controlled by transcription and stabilization of mRNA. A p53-independent pathway is suggested in X ray-induced apoptosis. (4) Radiation with heavy charged particles of 290MeV/u carbon-12 induced apoptosis of V79 cells with dose-dependent fashion. Relative biological effectiveness of carbon-12 for apoptosis induction showed a peak on the LET-RBE curve at 110 ke V/mum which was same as a peak for cell lethality. (5) Biopsy samples were obtained from radiotherapy patients who had uterine cervix malignancies, and stained by antibody against Ly^e antigens.Prognosis of patients who showed strong staining was significantly poorer in both local control rates and remote metastasis than those who showed negative-week staining.
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