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Title: Analysis of cell division fidelity of human repair defective cell lines
Author: Haddad, F.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 1998
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In this study the fidelity of cell cycle division in terms of fidelity of chromosome segregation was analysed in cell lines from Xeroderma pigmentosum groups A & D, and Trichothiodystrophy cell lines with comparison with a normal human fibroblast cell line. The XP and TTD cell lines, are both defective in nucleotide excision repair with susceptibility to skin cancer in the case of XPs but not the TTDs. The study was conducted using a micronucleus assay of cytokinesis-blocked binucleated cells combined with the kinetochore labelling technique and FISH for centromeric regions of two specific chromosomes (16 & 18). Analysis was performed in two different protocols, one assessing chromosome loss and the other one measuring chromosome non-disjunction after exposure of the cells to doses of colcemid and vinblastine. In the first protocol the ability of cell lines for regaining the division fidelity after several cell cycles was also determined. Data showed that XP and TTD cell lines were more sensitive to chemical-induced chromosome non-disjunction compared to a normal human cell line. Chemicals induced chromosome-loss in all normal and NER defective cell lines. However, in the case of XPD cell lines, the frequencies remained stable while frequency was reduced for normal and XPA cell lines. The results indicated that XP and TTD cell lines were defective in NER as well as in mechanisms monitoring the fidelity of cell cycle division. The possible relationship of p53-mediated checkpoint/apoptosis and defective transcription in XPD mutated cell lines was discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available