Thesis (MTech(Medical Technology))--Cape Technikon, Cape Town, 1996 / 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 supercoil.ing. 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.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:cput/oai:localhost:20.500.11838/1493 |
| Date | January 1996 |
| Creators | La Cock, Charles JR |
| Publisher | Cape Technikon |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Rights | http://creativecommons.org/licenses/by-nc-sa/3.0/za/ |
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