Antioxidant enzyme activity in murine hematopoietic bone marrow following treatment with interleukin 1 alpha: influence of tumor.
To determine whether non-hematologic tumors influence the bone marrow's antioxidant enzyme response to the radioprotective cytokine interleukin 1 alpha (IL-1), studies were undertaken using BDF1 and Balb/c mice bearing small, medium or large Lewis lung carcinoma (LLCa) or EMT6 mammary carcinoma tumors, respectively. Results demonstrated that, similar to nontumor-bearing mice, treatment of tumor-bearing animals with IL-1 was associated with a significant increase in marrow MnSOD activity. However, the duration of this elevated activity was reduced as tumor burden increased, and this reduction may have an impact on IL-1's ability to radioprotect tumor bearing animals, especially when tumor burden is large. In addition to cytokine-mediated responses, significant tumor-related influences on the marrow's antioxidant enzyme status were seen. Notably, it was observed that the presence of tumor was correlated with a marked suppression of antioxidant enzyme activity. Surprisingly, however, the pattern of enzyme suppression was found to differ between the two tumor models studied both in temporal onset and in the number of enzymes involved. In conclusion, the data obtained from these studies on tumor-bearing animals demonstrate that there are both cytokine-related and tumor-related influences which can effect the antioxidant enzyme status of the hematopoietic marrow-influences which may have the potential to alter the marrow's ability to tolerate free radical-generating events, both endogenous (i.e inflammation, infection) and exogenous (i.e. radiation, certain chemotherapeutic drugs) in origin.
Johnke
R M
RM
Department of Radiation Oncology, East Carolina University School of Medicine, Greenville, North Garolina 27858, USA.
Abernathy
R S
RS
Kovacs
C J
CJ
Evans
M J
MJ
Biggs
L E
LE
Daly
B M
BM
Loven
D P
DP
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002374:Catalase / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*
D007375:Interleukin-1; D011994:Recombinant Proteins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase