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 after administration of IL-1 alpha (0.5 micrograms/mouse, ip) and characterized by increases in D(o), Dq, 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-1 alpha 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(o), 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 and in vitro in our models, the mechanisms by which such responses modulate tumor radiosensitivity in vivo and in vitro are likely quite different.
Braunschweiger
P G
PG
Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Florida 33101, USA.
Basrur
V
V
Santos
O
O
Adessa
A
A
Houdek
P
P
Markoe
A M
AM
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects; D002999:Clone Cells; D004357:Drug Synergism; D000860:Hypoxia / Q000378:metabolism; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000532:radiotherapy; D011833:Radiation Injuries, Experimental; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D011994:Recombinant Proteins; D013482:Superoxide Dismutase / Q000378:metabolism; D000077704:Tirapazamine; D014227:Triazines / Q000008:administration & dosage; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014916:Whole-Body Irradiation
D007375:Interleukin-1; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; D011994:Recombinant Proteins; D014227:Triazines; D000077704:Tirapazamine; D002374:Catalase; D013482:Superoxide Dismutase