Influence of Animal Passage on a Line of Tissue-Culture Cells

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Abstract
This study confirms and further elucidates a previous observation that mouse passage increases the tumor-producing capacity of a low tumor-producing line of mouse tissue-culture cells. The change in the cells was maintained during serial passage of the cells in vivo and persisted for several months after return to culture. The increased tumor-producing capacity ultimately subsided, partially in one strain and almost completely in another after 8 months in vitro. The cells before and after mouse passage did not differ significantly with respect to their morphology in vitro or in vivo, their failure to elicit an early vascular response in the host, their antigenicity for mice of the strain of origin (C3H), or their low rate of anaerobic glycolysis in vitro. Chromosomal numbers were slightly altered. The cells after mouse passage did seem to differ in their increased resistance to the immunity they induced in the host. This effect was produced not only in cells cultured on stock medium but also in cells cultured on a different medium known to enhance the transplantability of the cells. Two cell strains were isolated after mouse passage that exhibited the morphologic, metabolic, and physiologic characteristics of another line of cells carried independently from the low tumor-producing line but originated in vitro from the same cell. The observations suggest that this cell type was present in culture before mouse passage and was selectively concentrated during mouse passage. Several possibilities to explain the increased tumor-producing capacity of the cell population after mouse passage are discussed.