Radioresistance in murine solid tumors induced by interleukin-1
- Univ. of Miami School of Medicine, Miami, FL (United States)
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{sub 0}, D{sub 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-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{sub 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. 32 refs., 6 figs., 1 tab.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 387312
- Journal Information:
- Radiation Research, Vol. 145, Issue 2; Other Information: PBD: Feb 1996
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
APPLIED STUDIES
55 BIOLOGY AND MEDICINE
BASIC STUDIES
NEOPLASMS
RADIOTHERAPY
MICE
RADIOPROTECTIVE SUBSTANCES
TIME DEPENDENCE
TUMOR CELLS
RADIOSENSITIVITY
ANOXIA
BIOLOGICAL RADIATION EFFECTS
RADIATION DOSES
RADIATION DOSE DISTRIBUTIONS
DOSE-RESPONSE RELATIONSHIPS
X RADIATION
LYMPHOKINES
ANTIOXIDANTS