| Project/Area Number |
01570541
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Yokohama City University |
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Principal Investigator |
NATSUYAMA Shusuke Yokohama City University, School of Medicine, Professor, 医学部, 教授 (20045983)
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| Co-Investigator(Kenkyū-buntansha) |
KAJIGAYA Yasuhiko Yokohama City Univetsity, School of Medicine, Staffs, Pediatric Physician, 医学部, 診療医
IKUTA Koichiro Yokohama City University, School of Medicine, Instructor, 医学部, 講師 (80159590)
SASAKI Hideki Yokohama City University, School of Medicine, Instructor, 医学部, 講師 (50106316)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Induction of differentiation / Myelomonocytic leukemia / G-CSF / Mitoxantrone |
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| Research Abstract |
We studied the action of the induction of differentiation by mitoxantrone (MIT) and recombinant human G-CSF (rhG-CSF) on murine myelomonocytic leukemia cell line WEHI-3B(D+). In a liquid culture, regardless of the cell concentration of WEHI-3B(D+), a tendency towards differentiation to mature myeloid cells of WEHI-3B(D+)cells due to MIT was observed and a reinforcement tendency of the induction of nitroblue tetrazolium reducing capacity as well as of ASD chroloacetate esterase staining was observed. By using rhG-CSF at low cell concentrations no induction of differentiation was observed. Since at concentrations of WEHI-3B(D+)cells of less than 1x 10^5/ml induction of differentiation was observed due to MIT, it is suggested that its mechanism of action differs from that of the induction of differentiation of G-CSF and is due to the direct action of MIT. We studied the effect of MIT on the proliferation and differentiation of cells from patients with newly diagnosed acute nonlymphocytic leukemia (ANLL). Fresh ANLL cells classified as M4 were induced by MIT to undergo terminal differentiation to macrophage-like cells. Finally we have compared the effects of rhG-CSF and mitoxantrone and examined the effects of exposing WEHI-3B-Y1 leukemia cells cultured in a protein-free medium to both compounds simultaneously. We found that combining rhG-CSF and mitoxantrone resulted in greater granulocytic differentiation of WEHI-3B-Y1 cells than did either compound alone in protein-free culture. In addition, nitroblue tetrazolium reducing capacity were induced by both agents in an additive manner. These studies demonstrate that separable events accompany the granulocytic differentiation of WEHI-3B-Y1 cells induced by different inducers.
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