Cytokinetics of tumour and endothelial cells and vascularization of lung metastases in C3H/He mice.

A model of lung metastases was developed using intravenous injection of tumour cell aggregates of spontaneous C3H/He mammary tumours in syngeneic mice. The growth rate of lung tumours decreased with increasing tumour volume with mean host survival of 46 days. The cytokinetics of individual tumours ranging between 0.004 and 4.2 mm3 in volume were studied. The labelling index (LI) ranged between 12 and 17%, the DNA synthesis time (Ts) being 9-10 hr. The growth fraction (GF) ranged between 26 and 38%. The cell cycle time (Tc) was found to be 18-19 hr. The LI and the GF decreased with increasing tumour volume doubling time (Td). No correlation was found between the tumour volume and Tc. The LI of endothelial cells within these tumours, ranging between 0.004 and 4.2 mm3 in volume was 14-15% and endothelial cell proliferation was not affected by tumour growth. Vascular parameters were also determined for these tumours as a function of tumour volume. Vascular volume increased with increasing tumour size while the percentage of capillary vessels decreased. The cellular volume to capillary volume ratio increased with increasing tumour volume. Necrosis was observed in 0.27 mm3 tumours and increased with increasing tumour size. The results from these studies suggested that the age-dependent decrease in proliferative activity of tumour cells growing in the lung is related to change in effective vascularity.