Radioresistance in murine solid tumors induced by interleukin-1

Interleukin-1 (IL-1) has radioprotective activity in hematopoietic lineages and in other normal cell renewal systems, but little is known about the effects of IL-1 alpha on the radiosensitivity of tumor cell populations, The present studies were conducted to investigate the effects of IL-1 alpha on the radiosensitivity of clonogenic cells in RIF-1 and SCC-7 tumors, Radioresistance was detected within 2-4 h after administration of IL-1 alpha (0.5 mu g/mouse, ip) and characterized by increases in D-0, D-q, alpha/beta and SF2. This radioresistance was similar to that seen in tumors rendered totally hypoxic before X irradiation. Tirapazamine, a hypoxic cell cytotoxin, and IL-la had synergistic schedule-dependent antitumor activity in vivo, suggesting that IL-1-induced radioresistance in vivo is due to hypoxia. Radioresistance induced by IL-1 alpha was transient, and the data suggested reoxygenation within 12 h. In vitro, IL-1 alpha had no direct effect on the radiosensitivity of SCC-7 cells in tissue culture under aerobic conditions, However, an increase in D-0, alpha/beta and SF2 was seen in clonogenic tumor cells from primary cultures treated with IL-1 alpha under aerobic conditions. Superoxide dismutase and catalase prevented the induction of radioresistance by IL-1 alpha in vitro, suggesting that oxidative responses from tumor macrophages after administration of IL-1 alpha may be responsible for induced radioresistance by IL-1 in vitro, Although oxidant stress induced by IL-1 may play an important role in the activity of IL-1 alpha both in vivo and in vitro in our models, the mechanisms by which such responses modulate tumor radiosensitivity in vivo and in vitro are likely quite different. (C) 1996 by Radiation Research Society.