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-1α on the radiosensitivity of tumor cell populations. The present studies were conducted to investigate the effects of IL-1α on the radiosensitivity of clonogenic cells in RIF-1 and SCC-7 tumors. Radioresistance was detected within 2-4 h after administration of IL-1α (0.5 μg/mouse, ip) and characterized by increases in D(o), D(q), α/β and SF2. This radioresistance was similar to that seen in tumors rendered totally hypoxic before X irradiation. Tirapazamine, a hypoxic cell cytotoxin, and IL- 1α had synergistic schedule-dependent antitumor activity in vivo, suggesting that IL-1-induced radioresistance in vivo is due to hypoxia. Radioresistance induced by IL-1α was transient, and the data suggested reoxygenation within 12 h. In vitro, IL-1α had no direct effect on the radiosensitivity of SCC-7 cells in tissue culture under aerobic conditions. However, an increase in D(o), α/β and SF2 was seen in clonogenic tumor cells from primary cultures treated with IL-1α under aerobic conditions. Superoxide dismutase and catalase prevented the induction of radioresistance by IL-1α in vitro, suggesting that oxidative responses from tumor macrophages after administration of IL-1α 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-1α 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.
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging