CHANGES IN THE EXTENTS OF VIABLE AND NECROTIC TISSUE, INTERSTITIAL FLUID PRESSURE, AND PROLIFERATION KINETICS IN CLONE-A HUMAN COLON-TUMOR XENOGRAFTS AS A FUNCTION OF TUMOR SIZE

Total, viable and necrotic tumour tissue, tumour cell yields, and colo ny forming efficiencies were measured in clone A human colon tumour xe nografts as neoplasms grew from about 100mm(3) to about 6000mm(3). The volumes of the total, viable and necrotic compartments were fit using the Verhulst equation to obtain estimates of growth rates and maximal sizes of the various compartments (carrying capacities). Additionally , at four discrete tumour volumes (250, 850, 2500 and 5500 mm(3)), hyp oxic percentages, proportions of parenchymal tumour and host cells, in terstitial fluid pressures, and proliferation kinetics including measu rements of apoptosis were determined. There were interesting relations hips between the shapes of the curves for total, viable and necrotic t issue to some of the other endpoints measured. Specifically, the volum etric growth curves for the total and viable tumour tissue compartment s were identical to a volume of approximately 1000 mm(3), but diverged at larger sizes, with the viable cell compartment exhibiting a smalle r carrying capacity. The shape of the growth curve for the necrotic co mpartment exactly mimicked that for the total volume compartment, but was delayed in time by about 21 days. Similarity in shape to that of t he overall tumour volume/necrotic volume curves was also seen for the curve for the increase in interstitial fluid pressure, and for the inc rease in the size of the host cell compartment. In contrast, the growt h of the hypoxic compartment and of the parenchymal tumour cell compar tment were similar in shape to that of the viable compartment. These d ata indicate that these compartments are functionally linked. Marked c hanges in cell kinetic parameters occurred as tumour size increased fr om 250-5500 mm(3). The labelling index and growth fractions decreased from 0.256-0.125, and 0.77-0.40 respectively, and the cell loss factor increased from 0.52-0.74. The volumetric and potential doubling times increased from 4.3-17.6 and 2.1-4.6 days respectively. The cell kinet ic changes could not be clearly related to the changes in shape of eit her the overall tumour volume or the viable tumour volume.