| A transplantable murine tumor model system has been established in our laboratory to study the contribution of the tumor microenvironment in tumor progression using the hypoxanthine phosphoribosyltransferase (HPRT) gene as a marker of chromosome fragmentation or loss. MN-11 was identified as the most stable clone with a low spontaneous mutant frequency (MF) and 1000 times increased sensitivity than the parental line in detecting mutagenic events induced by ;Histochemical analysis of MN-11 tumors showed the presence of granulocytes, macrophages, mast cells and lymphocytes. Biochemical measurements of total nitric oxide synthase (NOS) activity in tumor homogenates demonstrated a positive correlation between NOS activity and MF. The expression of inducible (iNOS) was estimated by Western blot analysis and localized by immunohistochemistry, The synthase was present in some tumors as a 130 kDa band, similar to the human iNOS, but not in others. The iNOS-positive cells included predominantly granulocytes and not tumor cells, lymphocytes or vascular endothelial cells. Granulocytes were found mainly in necrotic areas, less frequently in non-necrotic and at the periphery of the tumor. Positive correlations were observed between the number of infiltrating granulocytes and MF, and between % tumor necrosis and MF. These results are consistent with the notion that endogenously generated nitric oxide (NO;A series of nitrogen monoxide (NO)-donating drugs that differed in their rate of NO... |
