Studies on the enhancement by cyclophosphamide (NSC-26271) of artificial lung metastasis after labeled cell inoculation.

In a mouse model the retention of125I-5-iodo-2' -deoxyuridine-labeled tumor cells in the lung after iv injection was compared with the formation of tumor colonies in the lung 15 days after injection. The modification in lung retention after treatment with cyclophosphamide (CP), isophosphamide, Corynebacterium parvum, and heparin paralleled the changes in lung-colony numbers by these treatments. Since the modifications could be identified as early as 1 hour after iv administration of tumor cells, further evidence was obtained for the conclusion reached earlier that the modification of lung metastases by CP and Corynebacterium parvum is not due to immunologic mechanisms. Comparison with the lung retention of heat-killed tumor cells and living embryonic cells showed that CP induced an increased retention of all three cell types. In contrast, Corynebacterium parvum decreased the retention of living tumor cells, but failed to modify the retention of dead tumor cells, but did not affect the retention of living embryonic cells. Since no similar cell types were affected by the various treatments it seems likely that different mechanisms are involved. Apparently CP decreases the nonspecific resistance against the lodging and growth of any type of cell in the lung.