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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Regulation of haematopoietic stem cycle (CFU-S) proliferation in irradiated mice

Ali, Abdul Rabbi Manaf January 1986 (has links)
It has been suggested that the proliferation of haematopoietic stem cells (CFU-S) in mice is controlled by the balance of inhibitory and stimulatory factors. In normal mice about 10 percent of the CFU-S population are in DNA synthesis. It has been suggested that a high concentration of inhibitor blocks CFU-S from entering into DNA synthesis. Following damage by cytotoxic agents such as drugs or irradiation about 30 - 50 percent of CFU-S were in DNA synthesis and also stimulator was shown to be present. In this study the entry of CFU-S into DNA synthesis following low and sub-lethal doses of whole body X-irradiation has been studied. Furthermore the stimulator producing cells were also characterized. The number of CFU-S in bone marrow was not affected following exposure to a dose of 0.5 Gy. However the number of committed progenitors for the granulocyte/macrophage lineage was significantly reduced. The percentage of CFU-S in DNA synthesis was found to increase to 37.0+/- 7.0 percent at 30 minutes and 43.9+/-11.2 percent at 2 hours from that observed in unirradiated mice. However at 6 hours the percentage was 14.8 8.1 percent. At a sub-lethal dose of 4.5 Gy, the percentage of CFU-S in DNA synthesis increased to 34.0+/-14.0 percent at 6 hours after exposure, however before this time the percentage remained at a similar level to unirradiated control mice. When plugs of bone marrow were irradiated in-vitro at 0.5 Gy and 4.5 Gy doses, the time of CFU-S entering into DNA synthesis was the same as following in-vivo irradiation. The dose response curve of CFU-S entering into DNA synthesis when measured at 2 hours after exposure showed that the percentage was increased as the dose was increased and reached 30-50 percent at a dose of 0.5 Gy. Above this dose the CFU-S population was not stimulated at this time. When the percentage of CFU-S in DNA synthesis was measured at 6 hours after exposure, the values were the same as control for doses less than 0.5 Gy and above this dose the values were 30-50 percent. The presence of stimulator in bone marrow after irradiation was found to parallel the proliferative activity of CFU-S. The CFU-S population obtained 1 hour after 1.5 Gy was shown not' to respond to stimulator as CFU-S from normal bone marrow dia. The conditioned media prepared from bone marrow of mice Irradiated at 9.0 Gy (1 to 5 days post Irradiation) increased the proportion of CFU-S from normal bone marrow in DNA synthesis to 30-50 percent. The depletion of Thy1.2+ cells from regenerating bone marrow did not affect the ability to produce stimulator. However when Fc+ and Ia-2k+ cells were removed the stimulator production was affected. This suggests that the stimulator producing cells were radioresistant, Thy1.2-, Fc+ and Ia-2k+.

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