The growth and cell population kinetics of spontaneous tumours in domestic animals.

Abstract

INVESTIGATIONS into the relationship between cell proliferation and overall tumour growth rate in human cancer have to contend with the major limitation that only rarely can both cell kinetic data and information on volume growth rate be obtained in one and the same patient. When a case is operable it is usually inadvisable to delay treatment in order to estimate growth rate; when, for instance in the case of lung secondaries, it is right to leave tumours untreated, tissue specimens are seldom available.It was to overcome this limitation that the present investigations were begun. In many cases of malignant disease in domestic animals the natural history and histopathological features are very similar to human cancer and in a proportion of these cases it is permissible to observe the course of the disease and perform simple investigations before treatment or euthanasia. The present communication covers the first nine cases which have been studied in this project.The available data on the overall growth rate of untreated tumours in man have been reviewed by Steel and Lamerton (1966). The cases from which these data have been obtained form a highly selected group and one must be cautious in taking them to be typical of the majority of tumours, especially tumours in other anatomical sites. Some idea of the distribution of human tumour volume doubling times can be gained from the histogram shown in Fig. 1. This histogram shows the spread of 175 measurements of human tumour growth rate; 135 of these were metastatic deposits in the lung (Collins, 1962;Collins, Loeffler and Tivey, 1956;Breur, 1966); 34 were primary lung tumours; 6 were primary bone tumours (Spratt, 1965 Steel and Lamerton (1966) and compared with the available data on human tumour growth rate. The conclusion from this work was that in the majority of human tumours, cell loss could be the dominant factor determining growth rate. The same conclusion has been reached by Iversen (1967) and Refsum and Berdal (1967) on the basis of measurements of mitotic rate in tumours of the head and neck by the colchicine method; their calculations implied that the rate of cell loss must in their sample of tumours be in excess of 90% of the rate of cell production.

Thymidine Labelling Studies in a Transmissible Venereal Tumour of the Dog

“…What is remarkable is the failure of tritiated thymidine to label cells in regions of a tumour that show mitotic activity. So far as we are aware, the only previous report of such an observation (also in canine tumours) is that of Owen and Steel (1969). The main difficulty in establishing the existence of such a phe;nomenon is that in an autoradiograph there are always some cells that have a low grain count and which might be scored as labelled if the autoradiographic exposure time were increased.…”

“…There are good reasons for believing that in this tumour the growth limitation is caused by an immune reaction of the host against the TVT cells (Sticker, 1906;DeMonbreun and Goodpasture, 1934;Powers, 1968;Cohen, 1971 Growth limitation of the transmissible venereal tumour does not greatly influence the timing of the mitotic cycle of tumour cells. This is well established for G2 and S and there was no evidence for a lengthening of G1 or the whole cell cycle in the more slowly growing tumours.…”

“…1). The thymidine labelling experiments were performed essentially as described by Steel, Adams and Barrett (1966) and Owen and Steel (1969). Each dog was injected intravenously with 3 mCi of tritium-labelled thymidine (thymidine-6-T(n) TRK61, specific activity in excess of 10 Ci/mM, Radiochemical Centre, Amersham).…”

Immunohistochemical detection of a hypoxia marker in spontaneous canine tumours

“…Studies with transplantable rodent tumours (Hirst et al, 1982) have shown that tumour cells migrate from oxygenated to hypoxic regions at a rate of 1.1-2.2 jm h-as cells close to capillaries proliferate and hypoxic cells distant to capillaries are displaced into adjacent necrotic regions. While the mean potential doubling time for spontaneous canine tumours (5.4 ± 2.9 days; range 2.3-16 days) (Owen & Steel, 1969) is much greater than that for rodent tumours (1-2 days) and the cell migration rate in the spontaneous tumours might, therefore, be expected to be much lower, the possibility that previously well-oxygenated cells had migrated into the hypoxic regions by the end of the 24 h labelling period cannot be completely ruled out. The effect would be an apparent decrease in the hypoxic fraction because labelled hypoxic cells lost to necrosis would not have been counted in the morphometric analysis.…”

“…The widespread occurrence of labelled cells in the spontaneous tumours in the absence of necrosis might have been interpreted to mean that cell migration processes were not occurring. However, the overall cell loss factors for rodent and spontaneous canine tumours are similar (Hirst et al, 1982;Owen & Steel, 1969) so that mechanisms of cell loss other than cell migration into necrotic regions may exist.…”