Soluble factors produced by normal or tumor cells, inhibiting the uptake of 5-iodo-2′-deoxy-uridine by cancer cells in vitro

The uptake of ¹²⁵I-5-iodo-2′-deoxy-uridine (¹²⁵IUdR) by lymphoma cells is inhibited in lethally irradiated hosts incompatible for Hh (hemopoietic-histocompatibility) loci. In the course of attempts to reproduce this phenomenon in vitro, a soluble factor (uptake inhibiting factor, or UIF) was found in the supernatant of cultured (16 hr, 37°C) spleen cells. UIF was produced by non-stimulated splenocytes of various strains of conventional and athymic (nude) mice and rats and by various tumor lines as well. UIF was found to be non-strain, non-species and non-tissue specific, since it was capable of inhibiting the ¹²⁵IUdR uptake of mouse, hamster and human tumor cells of various tissue origins. Lethal irradiation, silica or IDF (immunodepressive factor) treatment of donor mice, or irradiation or treatment with actinomycin D of spleen cells in vitro, did not prevent UIF production by such cells. On the other hand 5-fluoro-2′-deoxy-uridine (FUdR) reduced UIF production by 50%. UIF was found to be relatively resistant to heat and proteolytic enzymes in vitro. In addition UIF was capable of cytostatic or cytotoxic effects on tumor cells in tissue culture. UIF-like activity was found also in the plasma of tumor bearing mice. The biological role of UIF seems to be uncertain. Nevertheless it could interfere markedly with in vitro assays involving cell proliferation monitored by DNA-precursor uptake.