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 interleu kin 1 alpha (IL-1), studies were undertaken using BDF1 and Balb/c mice bearing small, medium or large Lewis lung carcinoma (LLCa) or EMT6 ma mmary carcinoma tumors, respectively. Results demonstrated that, simil ar to nontumor-bearing mice, treatment of tumor-bearing animals with I L-I was associated with a significant increase in marrow MnSOD activit y. However; the duration of this elevated activity was reduced as tumo r burden increased and this reduction may have an impact on IL-1's abi lity to radioprotect tumor bearing animals, especially when tumor burd en is large. In addition to cytokine-mediated responses, significant t umor related influences on the marrow's antioxidant enzyme status were seen. Notably, it was observed that the presence of tumor was correla ted with a marked suppression of antioxidant enzyme activity. Surprisi ngly, however, the pattern of enzyme suppression was found to differ b etween 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 cyto kine-related and tumor-related influences which can effect the antioxi dant enzyme status of the hematopoietic marrow - influences which may have the potential to alter the marrow's ability to tolerate free radi cal-generating events, both endogenous (i.e inflammation, infection) a nd exogenous (i.e. radiation, certain chemotherapeutic drugs) in origi n.