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Departments of Immunology and Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee
The antitumor activity of guinea pig serum fractions was studied in vivo and in vitro by bright field, fluorescence, and electron microscopy observations and by dye permeability and cytidine-3H incorporation in 6C3HED lymphosarcoma cells. In C3H mice bearing the ascites tumor treated with the L-asparaginase fraction, there was a decrease in the total number and mitosis of tumor cells, a reduction in the cytoplasmic fluorescence (RNA), and a rise in the number of macrophages and phagocytosis of tumor cells. Anti-6C3HED isoantibodies were not detected in their sera. The L-asparaginase fraction of guinea pig serum had in vitro cytotoxic activity on surviving cell cultures of 6C3HED lymphoma cells in a medium deprived of L-asparagine. Uptake of cytidine-3H by tumor cells was found to be a more quantitative and sensitive method than the dye permeability test for measurement of the in vitro cytotoxic activity. A reduction in cytidine-3H uptake in most tumor cells after 24 hr of in vitro treatment was found by radioautography. These results indicate that the L-asparaginase fraction of guinea pig serum has in vivo and in vitro antitumor activity. In vitro, this fraction acts directly on the tumor cells; hence, the in vivo host macrophage response and phagocytosis of structurally normal cells appears to be a secondary, nonspecific phenomenon.
1 This work was supported in part by National Cancer Institute Grants CA 07594 and CA 06660-03, and by the American-Lebanese-Syrian Associated Charities (ALSAC).
Received 1/ 7/66. Accepted 6/27/66.
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