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Mitochondrial DNA heteroplasmy in radiation induced myelodysplasia and leukaemia

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dc.creator La Cock, Charles JR 2013-02-26T06:15:16Z 2016-02-22T04:58:57Z 2013-02-26T06:15:16Z 2016-02-22T04:58:57Z 1996 2018-06-24T05:12:26Z 2018-06-24T05:12:26Z
dc.description Thesis (MTech(Medical Technology))--Cape Technikon, Cape Town, 1996
dc.description Haematol.ogical defects observed in cl.onal deletions of mtDNA and the inhibition of mitochondrial function by benzene and chloramphenicol., suggest a role for mtDNA in the pathogenesis of radiation - induced preleukaemia (MDS). The fact that leukaemia cell.s contain abnormal mitochondria and abnormally structured mtDNA, makes it reasonable to assume mtDNA mutations could be central to the pathogenesis of both MDS and l.eukaemia. It was decided to examine MDS patients for the presence of mtDNA length mutations (dimers and cocantameres). Such topol.ogical forms have already been reported in the literature in association with human leukaemia. These steric considerations suggest that mtDNA dimers are probably non-functional due to Thus, it was felt that a progressive accumulation of non-functional dimers in the haematopoietic compartment could account for many of the cl.inical. features associated with MDS. Transmission electron microscopy was used to examine haematopoietic mtDNA in the bone marrow of six patients with MDS. Abnormal mtDNA dimer formation was found in al.l instances. The proportional. number of these dimers were found to roughly correlate with the Myeloid/ Erythroid cell. ratio in the bone marrow, and it appeared likely that the dimers were generated in the myeloid compartment during early MDS. Control.l.ed radiation studies were performed on 20 wistar rats in an attempt to elucidate the approximate time when abnormal mtDNA dimer formation occurred, fol.l.owing fractionated gamma or gamma-neutron irradiation. Gamma-irradiated rats demonstrated abnormal mtDNA dimer formation at the time hypoplastic marrow recovery was first observed.
dc.language en
dc.publisher Cape Technikon
dc.subject Hematological manifestations of general diseases
dc.subject Mitochondrial DNA -- Abnormalities
dc.subject Myelocytic leukemia
dc.subject Medical technology
dc.title Mitochondrial DNA heteroplasmy in radiation induced myelodysplasia and leukaemia
dc.type Thesis

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