Altered radioprotective properties of interleukin I alpha (IL-1) in non-hematologic tumor-bearing animals.
The radioprotective properties of IL-1 were investigated in the respective murine hosts for the Lewis lung (LLca) and EMT-6 tumors. For these studies, doses of total body irradiation were selected for the C57B1/6 (9.5 Gy) and Balb/c (7.5 Gy) mice that resulted in a 60% mortality over a 30-day interval. When a "priming" dose of 2.5 x 10(5) U IL-1 was administered 24 hr prior to the radiation exposure, animal mortality was markedly reduced (60% vs 5-10%). Under identical experimental conditions, however, the presence of either the LLca or the EMT-6 tumors in their respective host strains was found to compromise the level of radioprotection conferred by this priming dose of IL-1. In Balb/c mice bearing the EMT-6 tumor, a priming dose of IL-1 resulted in only a modest level of radioprotection when compared to non-tumor-bearing control animals (median animal survival increased by 11.5 days). In C57B1/6 mice bearing the LLca tumor, IL-1 failed to demonstrate any evidence of radioprotection. Following a sublethal dose of total body irradiation, the appearance of an accelerated repopulation of the stem cell (8d CFUs and CFU-GEMM) and the myeloid progenitor (CFU-M) compartment in the marrow of the IL-1 primed EMT-6, but not the LLca, tumor-bearing animals was consistent with the hypothesis that the mechanism leading to radioprotection in IL-1 primed rodents involves an accelerated recovery of hematopoietic activity. It was also noted that the presence of the EMT-6 tumor was associated with an increase in the "radiosensitivity" of the Balb/c mouse. Collectively, these data suggest that the use of biological modifiers should be examined under altered physiological conditions prior to attempting to translate them into the clinic.
Kovacs
C J
CJ
Department of Radiation Oncology, East Carolina University School of Medicine, Greenville, NC 27858.
Gooya
J M
JM
Harrell
J P
JP
McGowan
K M
KM
Evans
M J
MJ
D000818:Animals; D003131:Combined Modality Therapy; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D007375:Interleukin-1 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008325:Mammary Neoplasms, Experimental / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011994:Recombinant Proteins; D014916:Whole-Body Irradiation
D007375:Interleukin-1; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins