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Title: Radiation induced aneuploidy in somatic cells
Author: Hermine, T.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 1998
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This thesis describes the cytogenetic effects of X-irradiation on chromosome segregation. Metaphase analysis of G0 irradiated human lymphocytes showed that X-irradiation resulted mainly in structural aberrations but that non-disjunction (measured as chromosome gains) and polyploidy were also induced. The technology used involved fluorescence in-situ hybridisation with whole chromosome probes for chromosomes 2 & 8. Radiation induced micronuclei were measured in both human fibroblasts and Chinese hamster cell lines using the cytokinesis block micronucleus assay coupled with kinetochore labelling. The results confirmed the clastogenic properties of X-rays with a large induction of kinetochore negative micronuclei. X-rays were also shown to have a small aneugenic activity through significant induction of chromosome lagging (kinetochore positive micronuclei). Cell cycle phase sensitivity studies in (HF12) showed that cells in the G2 or M phases of the cell cycle were more sensitive to the induction of whole chromosome lagging. In contrast, cells in G1 or S were more sensitive to the induction of acentric fragments. Micronuclei induction in the repair proficient (V79-4) and deficient (irsl, irs3) cell lines showed that non-DNA targets could be responsible for chromosome lagging in asynchronously dividing cells. In order to gain mechanistic information on micronuclei induction, an aneugen (podophyllotoxin) as well as an agent with both clastogenic and aneugenic activities (etoposide) were also tested within the same experimental system. The two chemicals gave identical responses in the three cell lines for micronuclei induction; podophyllotoxin as an aneugen and etoposide inducing both a clastogenic and an aneugenic response. However, the induction of multinucleated cells after podophyllotoxin treatment showed that irs3 repair defect might involve modification of a mitotic check point. The mechanisms of aneuploidy induction probably involve direct and indirect damage to the spindle components as well as disturbances of mitotic cellular ion regulation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available