Growth and cell proliferation kinetics of a marine plasmacytoma in relation to its environment
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Cell proliferation kinetics of plasmacytoma has been assessed in vitro and in vivo. The proliferation of plasmacytoma and other cell cultures in vitro has been assessed in terms of the culture environment, and humoral mediators (UIF) produced by cells of the central and peripheral lymphoid tissues. Foetal calf serum (FCS), has been demonstrated to influence DNA synthesis as assessed in terms of isotope uptake by cell cultures. The amount of radioactivity in the acid soluble and insoluble pools, was reduced as the concentration of FCS in the culture was increased. The relative change in isotope availability in both pools was approximately similar. The reduction of isotope activity in the acid soluble pool may suggest that FCS was interfering with the transport of isotope across the cell membrane; and the reduction of isotope activity in the acid insoluble pool may be a consequence to the effects observed in the acid soluble pool. The inhibition of isotope uptake by FCS may depend on several factors, such as, the batch of FCS, the type of cell culture under investigation, its culture density, culture incubation time and culture incubation sequence. FCS may interact with other substances available in the culture environment, either by increasing or decreasing the relative amount of isotope uptake by the respective cultures. The uptake of isotope by cell cultures that secrete polyamines into their culture environment which contains FCS, will consequently be reduced. The inhibitory effects of some UIF preparations on the uptake of isotope by cell cultures were modulated by FCS, and by the culture incubation sequence. The inhibitory effects of some of the fractions of UIF at some incubation sequences (with FCS), may be regarded as either "false positives" or the inhibition is a transitional one in the sense that it depended on the incubation sequence. Thus the interpretation in the change of radioisotope uptake must be viewed critically. UIF may contain heat sensitive substances, as the inhibitory effect of UIF 56c remained stable in both FCS environments and this may suggest that some factors in UIF which were heat sensitive were reacting with FCS to influence the inhibitory pattern of radioisotope uptake. Similarly the inhibitory effects of polyamines without FCS on the uptake of isotope by cell cultures, were evident when the culture incubation sequence was changed. Supernatants (UIF) produced by cells from the spleen, lymph nodes, bone marrow and thymus, were found to inhibit the uptake of isotope by cell cultures. The UIFS, which were obtained from the spleen, have demonstrated that the macrophage was the main source for the production of the inhibitory supernatants. The inhibitory material may contain a variety of substances, apart from thymidine, which may contribute to the regulation of cell proliferation. The growth kinetics of plasmacytoma in vivo, in two different immunological environments have revealed that tumour growth may also be controlled in T-cell deficient environments, as the latency period of tumour growth, was longer in the "nude" mice than in the normal counterparts Balb/c mice. Natural killer cells and macrophages may be some of the contributors to the suppression of tumour cell proliferation in the earlier periods of tumour growth. The growth kinetic studies of plasmacytoma in vivo, have demonstrated that the tumour birth rate was decreasing with increasing tumour age. Cell loss was approximately similar at the different stages of tumour growth, thus the growth fraction and the average intermitotic time may be influencing the cell production rate. The birth rate was assessed in terms of a weighted and unweighted least square regressions, to compare the reductions in error variability associated with the metaphase "Collection Function" curves, and its consequent effects on the standard errors of the respective Tea associated with each birth rate curve. In some birth rate curves the variance was generally proportional to the metaphase index, but in others the variance was not proportional. To reduce the error variability associated with the birth rate curves, other types of transforms may be required apart from the variance weighted transform.
Thesis, PhD Doctor of Philosophy
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