Segregational fidelity of chromosomes in human thyroid tumour cells |
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Authors: | E M Parry H Ulucan F S Wyllie D Wynford-Thomas J M Parry |
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Institution: | (1) School of Biological Sciences, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK, GB;(2) Cancer Research Campaign Thyroid Tumour Biology Research Group, Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK, GB |
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Abstract: | Using fluorescence in situ hybridisation (FISH) we have analysed the segregational fidelity of all the human chromosomes during
mitotic cell division. The losses and gains of chromosomes were analysed in human polyploid cell lines derived from a well-differentiated
papillary thyroid cancer. These thyroid cells can be cultured for more than 300 population doublings. For the purpose of our
study the polyploid nature of the cells may act as a protective buffer against the cell-lethal effects of the loss of individual
chromosomes. To evaluate the role of the p53 gene product in maintaining the fidelity of chromosome segregation we compared
the frequencies of chromosome loss and gain in cultures with wild-type p53 activity (K1E7neo3) and cultures transfected with
plasmids expressing a mutant p53 product (K1E7scx6). Cultures were analysed for the presence of both structurally normal and
rearranged chromosomes at both early and late passages. Cell cultures with defective p53 activity showed progressive chromosome
loss from a median chromosome number of 87–97 to 75–86. Cell growth in cultures with wild-type p53 activity showed the loss
of chromosomes 6, 7, and 8 and the gain of 17 and 20. Cultures expressing mutant p53 activity showed the loss of chromosomes
2, 5, 14 and 17 and the gain of 4 and 22. The combination of defective p53 and growth resulted in further destabilisation
with the additional losses of chromosomes 3, 11, 15, 16 and 21. Chromosomes 1, 9, 10, 12, 13, 18, 19, X and Y segregated stably
under all the culture conditions as did the structurally rearranged marker chromosomes. The study has demonstrated variation
in the fidelity of mitotic chromosome segregation and the influence of p53 gene activity upon the segregation of individual
human chromosomes.
Received: 7 August 1998; in revised form: 28 August 1998 / Accepted: 29 August 1998 |
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