Pattern of organ colonization of metastasizing mouse L929-MM4 cells and the stimulation of lung tumor formation by cyclophosphamide.

The pattern of lung colonization of L929-MM4 metastasis-derived cells was studied in C3HA/Hab mice. The incidence of mice with lung tumors and the number of tumor foci increased with the number of tumor cells in the i.v. inoculum until a 'plateau' was reached. However, some 30 per cent of the animals continued to show no macroscopic or microscopic evidence of metastases. Twenty days after the i.v. injection of 2.5 X 10(5) L929-MM4 cells, viable tumor cells were recovered from 80-90 per cent of the animals as judged by in vivo or in vitro assay methods, even though survival of mice under these conditions was 50 per cent at the end of a 3-month period. These results are discussed in relation to possible tumor dormant states. Cyclophosphamide stimulated both the incidence and the number of lung tumor foci after i.v. injection of tumor cells, if the drug was administered before the tumor cell inoculum. On the basis of the observed time dependency of this effect, and the low immunogenicity of L929-MM4 cells in C3HA/Hab mice, the results could be explained on the basis of drug damage to normal cells.