The colony-to-cluster ratio in agar cultures of bone marrow. I. Constancy under standardized conditions and alteration in tumour-bearing mice and by various inhibitors added in vitro.

The growth of granulocyte-macrophage colony forming cells (GM-CFC) from mouse bone marrow was studied in agar cultures in glass capillaries. Under standard conditions with normal bone marrow a specific total number of cell clones (colonies + clusters) and also a specific colony-to-cluster ratio (CClR) was found for each of 4 different mouse strains. Both parameters were studied in tumour-bearing mice and found to be influenced independently and, in part, in an opposite way. Thus, for bone marrow of mice with the Ehrlich ascites carcinoma an inhibition of clone formation was found whereas the growth of those clones still formed was stimulated (only colonies present). "Natural" inhibitors as present in uraemic serum added to the cultures decreased the number of clones without altering the CClR. The same is true for the inhibitors in CSF-containing endotoxin serum. On the other hand, inhibitors such as spermine or the synthetic 3'-deoxy-3'-fluorothymidine depressed the clone formation as well as the growth rate of the clones (relative increase of clusters and decrease of colonies). It is concluded that the sensitivity of the GM-CFC against various influences may differ from that of the cells in the clones they form; therefore, the determination of the CClR will provide a more refined interpretation of influences on the haematopoietic system.