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Title: Cell cycle studies during carcinogenesis in the hamster cheek pouch
Author: Nadarajathilagaratnam, Candiah
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1970
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The stratified squamous epithelia of the adult are typical examples of steady state renewal systems. The rate and location of mitosis, and the duration of the cell cycle and its phdses,are different in the various steady state systems as seen in those of the cheek pouch and the palate (Experiment 2). The only common feature shared by steady state systems is that the rate of cell production in these populations is in balance with their own rates of cell loss. While the progenitor cells were confined to the basal cell layer of the cheek pouch epithelium, mitotic figures and labelled cells were also observed in the suprabasal layers of the epithelium of the palate. pile it seems certain that about one -third of the progenitor cells in the palatal epithelium were present in the suprabasal layers, the nature of origin of these cells is uncertain, but has two possibilities. One is that these are stem type of cells that are inherently present in the suprabasal layers (page 44), and the other is that these are of the dividing transit type of cells originating from the basal cells, i.e. a proportion of the cells leaving the basal layer are capable of participating in the cell cycle. The latter suggestion does not compromise with the possibility that these are mitotic figures and labelled cells of the basal layer that are being pushed out of it as a result of population pressure. While about 20% of the labelled cells were present in the suprabasal layers of carcinogen induced regular epithelial hyperplasia (Experiment 4), this percentage had increased to about 44% in pre-neoplastic hyperplasia (Experiment 5B) of hamster cheek pouch. While cells that migrate out of the basal layer of the normal cheek pouch epithelium undergo regular maturation and keratinisation, during carcinogenesis a proportion of the cells leaving the basal layer retain the ability to undergo cell division. This proportion gradually increases as evidenced by the presence of twice as many labelled cells in the suprabasa.l layers of preneoplastic hyperplasia as there are in the suprabasal layers of early regular epithelial hyperplasia, ultimately leading to a loss of stratification so that the dividing and non - dividing cells become mixed with each other. There is a progressive increase in the number of cells in DNA synthesis and mitosis,to ether with an increase in the rate at which these cells progress through the cell cycle. This is accompanied by á progressive decrease in the duration of the cell cycle. While the above estimates for the duration of the phases of the cell cycle at different stages during carcinogenesis have shown that all the phases of the cell cycle are variable, the degree of reduction of the duration of each phase achieved at the different stages during carcinogenesis is not similar. The drastic reduction in the duration of the cell cycle from 163.9 hrs. in the normal cheek pouch to 15.4 hrs. is essentially due to shortening. of the duration of the Gl - phase from about 150 hours to 7.13 hours. In comparison to this, the reduction in the duration of the other three phases of the cell cycle during; development of squamous cell carcinomas amounts only to 5.32 hours. Th:s the earlier suggestion that the G1 -phase is the one of most variable duration remains tenable. It was found that vinblastine sulphate in a dose of 4 mg. per kg. body weight of the animal produced effective arrest of mitosis at the metaphase stage (Lxperiment 1). The estimates of the rate and duration of mitosis by the method of metaphase arrest by vinblastine (Experiments 4 & 5A) were close to the values obtained by tritiated thymidine autoradiography. However, the latter method allows much more valuable information to be gathered. The growth fraction of squamous cell carcinomas was found to be 0.62. Considering that the normal cheek pouch epithelium consists of 3 - 4 cell layers and that only the basal cells are capable of proliferation, then the ratio of the proliferating cells to the total number of cells (growth fraction) would be about 0.25 - 0.35. Thus the fraction of proliferating cells in tumours is greater than that of normal epithelium. The appearance of progenitor cells in the suprabasal layers of epithelial hyperplasia. prior to development of tumours and the increased number of proliferating cells per unit cell mass of the tumours indicate that there is delayed maturation and keratinisation of the population leading to more cells participating in the cell cycle. 1ullough (1965) suggests that delayed maturation and the progressive increase in the rate of generation of cells is possibly due to a progressive breakdown of the organisation of the tissue due to the gradual removal of the restraint on mitotic activity that is present in normal tissues.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available