Regulation of tumor development: the biphasic effects of silica and of lipopolysaccharide on natural resistance.

The impact on tumor development of the BRM silica and LPS was assessed through analysis of changes in NR parameters in vivo and in vitro. Although injection of the fumed silica Cab-o-sil 3 days before a threshold s.c. inoculum of L5178Y-F9 cells increased the tumor frequency in syngeneic DBA/2 mice, tumors recovered from silica-treated animals exhibited an augmented resistance to NAb and to in vivo NR. Cab-o-sil increased in vivo NR and induced a biphasic modulation of anti-tumor NAb and NK activities. The appearance of more autonomous tumors in Cab-o-sil-treated mice corresponding with a stimulation of NR parameters, suggests that the adjuvant activity of silica also contributes to its co-carcinogenic effect by accelerating tumor development. While injection of LPS 2-3 days before a threshold tumor inoculum lowered the tumor incidence, the survival of tumor cells injected within 1 day of LPS was increased. A corresponding early decrease in NAb activity occurred, in contrast with increases in NK cell and NAb levels previously observed after 5 days. This biphasic effect of LPS on NR effectors assayed in vitro was also seen on in vivo NR. Although their frequency was higher, tumors initiated during the period of LPS-induced NR abrogation exhibited greater reductions in NAb binding and sensitivity to NR than tumors from control mice. These data extend the support for NAb acting against tumor cells in vivo and reveal the dual nature of NR in tumor development, defending against small tumor foci and driving the progression of the surviving neoplasm.