1999 Fiscal Year Final Research Report Summary
Intracellular damage caused by anti-cancer drugs and radiation, analysis of regulatory mechanism of apoptosis in topoisomerase mutant cells
| Project/Area Number |
09670826
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Yokohama City University School op Medicine |
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Principal Investigator |
FUNABIKI Tetsunori Yokohama City University School of Medicine, Pediatrics, Assistant Professor, 医学部・付属病院, 講師 (20264616)
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| Co-Investigator(Kenkyū-buntansha) |
IKUTA Koichiro Yokohama City University School of Medicine, Pediatrics, Assistant Professor, 医学部・付属病院, 講師 (80159590)
SASAKI Hideki Yokohama City University School of Medicine, Pediatrics, Associate Professor, 医学部・付属病院, 助教授 (50106316)
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| Project Period (FY) |
1997 – 1999
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| Keywords | topoisomerase II / apoptosis / drug resistance / cell cycle |
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| Research Abstract |
(1) We established the method of quantification of apoptotic cells, i.e. BrdU was incorporated to fixed cells by TdT, and apoptotic cell were identified by enzyme linked immunoassay with anti-BrdU antibody conjugated with FITC.
(2) We quantified the apoptotic human leukemia cells which have wild type topoisomerase II (topo II) and drug-resistant sublines which carries mutation in topo II after the exposure of anti-cancer drugs. The degree of resistance to anti-cancer drug was inversely proportional to the number of apoptotic cells.
(3) We found that both of wild type cells and drug resistant cells accumulated in G2-M phase when treated with anti-topo II drugs such as doxorubicin or VP-16. Thus, doxorubicin and VP-16 seem to cause apoptosis of cells at G2-M phase.
(4) Recently the expression of topo II was shown to be down regulated before the apoptotic change of the cell. We examined the regulatory mechanism between cell cycle progression and the expression of topo II. The expression of topo II was slightly decreased in both wild type cell and drug resistant cell lines, one with low expression of normal protein and the other with wild type cell equivalent expression of mutant protein. These results suggested the existence of the apoptotic pathway which induced by the suppression of topo II activity.
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[Publications] Xiao-Tank Konng, Kohmei Ida, Hitoshi Ichikawa, Kimiko Shimizu, Misao Ohki, Nobuo Maseki, Yasuyuki Kaneko, Masahiro Sako, Yukio Kobayashi, Arinobu Tojou, Ikuo Miura, Harumi Tsunoda, Tetsunori Funabiki, Keizo Horibe, Hiroyuki Hamaguchi, Yuichi Akiyama, Fumio Bessho, Masayoshi Yanagisawa and Yasuhide Hayashi: "Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript"Blood. 90. 1192-1199 (1997)
Description
「研究成果報告書概要(欧文)」より
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