Suppressive Factors in Ascitic Fluids and Sera of Mice Bearing Ascites Tumors2

Abstract

Cell-free ascitic fluids from several mouse tumors (CFAF) and control ascitic fluids from control mice given injections of Freund's adjuvant (FAF) were assayed for: 1) regulatory activity on the uptake of tritiated thymidine or uridine by various cell lines during a 3-hour culture and 2) activity against normal mouse spleen cells responding to mitogens, as measured by tritiated thymidine uptake 48–54 hours after the onset of culture. Female mice of strains DBA/2J, C57BL/6J, and CBA/J and of white Swiss stock were used. Of the five distinct inhibitory activities characterized, the first was a dialyzable inhibitor of the uptake of tritiated uridine, but not thymidine, in 3-hour cultures. This inhibitor may be an endogenous nucleotide, possibly produced by the high RNA turnover of the tumor cells. The second was a dialyzable inhibitor of thymidine uptake in 3-hour and in 2-day cultures of stimulated spleen cells. The third was a factor in dialyzed CFAF-inhibited thymidine uptake by spleen cells cultured for 2 days with or without concanavalin A (Con A). This inhibitor was present in normal mouse serum; however, its concentration was apparently increased in the sera of mice bearing the ascites tumors. The fourth activity, which was heat-labile and present in ascitic fluids and normal sera, was demonstrable in spleen cell cultures containing Con A. This activity appeared to be mediated by an antibody-independent activation of the alternative complement pathway. The fifth inhibitor, which was labile at 56° C, was seen in FAF but not in CFAF. Its lack of identity with complement was confirmed by the failure of zymosan absorption at 37° C to influence the levels of inhibitory activity.