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The Incorporation of L-Asparagine-¹⁴C by Lymphoma 6C3HED Cells: Its Inhibition by Guinea Pig Serum¹

Department of Pathology, The New York Hospital-Cornell Medical Center, New York, New York

Lymphoma 6C3HED-OG cells (of Gardner's original line), growing intraperitoneally in susceptible C3H hosts, were found to take up L-asparagine-¹⁴C readily from subcutaneous depots. Further, the incorporation of L-asparagine-¹⁴C was almost completely prevented in vivo by the i.p. injection of heated serum procured from normal guinea pigs, which is known to exert antilymphoma effects on the OG cells and to contain active asparaginase even after heating at 56°C for 30 min. An opposite effect was obtained with normal horse serum, which does not have antilymphoma effects and is known to be devoid of asparaginase. By contrast, under identical conditions in vivo, the 6C3HED cells failed to take up L-aspartic acid-¹⁴C, or did so only poorly.

In vitro, the Lymphoma 6C3HED-OG cells also took up L-asparagine-¹⁴C avidly. Again, the incorporation of L-asparagine-¹⁴C was almost completely prevented by guinea pig serum, either unheated or heated at 56°C for 30 min, whereas horse serum had an enhancing effect. Similarly, too, the OG cells failed to take up L-aspartic acid-¹⁴C in vitro, or did so only sparingly.

The cells of Lymphoma 6C3HED-RG1, which, in contrast to the OG cells, are not susceptible to the antilymphoma effects of guinea pig serum in vivo and do not depend upon extrinsic L-asparagine for growth in vitro, also regularly incorporated L-asparagine-¹⁴C from subcutaneous depots in vivo. Further, guinea pig serum inhibited incorporation under such circumstances, and the RG1 cells did not take up notable amounts of L-aspartic acid in vitro.

The implications of the findings are briefly considered in relation to the metabolism of asparagine by Lymphoma 6C3HED cells of the 2 types and to the antilymphoma effects of heated guinea pig serum.

¹ Supported in part by grants from the American Cancer Society, the National Cancer Institute (Grant CA-6833), and Mr. John W. O'Boyle.

Received 6/16/65.