Fate of cultured cells after injection into the circulation of syngeneic animals.

In a model of metastasis, the fate of radioactively labeled cells cultured from spontaneous tumors was studied by i.v. injection into animals syngeneic with the tumor. Double isotope labeling of the cells produced a 14C/3H ratio that was used to identify putatively undamaged cells within the tissues. It was found that within 5 min of injection the cells concentrated almost exclusively in the lungs. In the following hours, these concentrations declined rapidly, and the change in 14C/3H ratio indicated that this decline was due to the death of the tumor cells. After 24 hr, only a small percentage of the injected radioactivity could be detected within the animal. Cells derived from two culture lines were traced in this manner. One cell line was derived from a spontaneous squamous carcinoma that does not metastasize in vivo, and a second was derived from a spontaneous adenocarcinoma that metastasizes readily in vivo. Despite the dissimilar behavior of the original tumors, these two cell lines displayed remarkably similar behavior after injection, especially if the cells were allowed to recover from trypsin treatment. Syngeneic neonatal fibroblasts were cul tured, and their behavior in this system was compared with the cells derived from the tumors. Regardless of the entirely differ ent origin and character of the fibroblasts, the same pattern of organ selectivity and cell death was seen. The data indicate that there is an apparently nonspecific mechanism within the animal by which nonhemopoietic cells are trapped in the lungs and rapidly destroyed.