In Vivo and in Vitro Effects of the L-Asparaginase Fraction of Guinea Pig Serum on the 6C3HED Ascites Lymphosarcoma1

The antitumor activity of guinea 1'ig 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 Lasparaginase fraction, there was a decrease in the total num ber 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 ix;rmeability test for measurement of the in vitro cyto toxic activity. A reduction in cytidine-'H 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 ap]>ears to lx?a secondary, nonspecific phenomenon.