RADIORESISTANCE IN MURINE SOLID TUMORS INDUCED BY INTERLEUKIN-1

Interleukin-1 (IL-1) has radioprotective activity in hematopoietic lin eages and in other normal cell renewal systems, but little is known ab out the effects of IL-1 alpha on the radiosensitivity of tumor cell po pulations, The present studies were conducted to investigate the effec ts 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 admi nistration of IL-1 alpha (0.5 mu g/mouse, ip) and characterized by inc reases in D-0, D-q, alpha/beta and SF2. This radioresistance was simil ar to that seen in tumors rendered totally hypoxic before X irradiatio n. Tirapazamine, a hypoxic cell cytotoxin, and IL-la had synergistic s chedule-dependent antitumor activity in vivo, suggesting that IL-1-ind uced radioresistance in vivo is due to hypoxia. Radioresistance induce d by IL-1 alpha was transient, and the data suggested reoxygenation wi thin 12 h. In vitro, IL-1 alpha had no direct effect on the radiosensi tivity of SCC-7 cells in tissue culture under aerobic conditions, Howe ver, an increase in D-0, alpha/beta and SF2 was seen in clonogenic tum or cells from primary cultures treated with IL-1 alpha under aerobic c onditions. Superoxide dismutase and catalase prevented the induction o f radioresistance by IL-1 alpha in vitro, suggesting that oxidative re sponses 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 activ ity of IL-1 alpha both in vivo and in vitro in our models, the mechani sms by which such responses modulate tumor radiosensitivity in vivo an d in vitro are likely quite different. (C) 1996 by Radiation Research Society.