Predisposition of [125I]5-iodo-2'-deoxyuridine-labeled normal and neoplastic mouse fibroblasts to lysis by normal macrophages.

During an investigation into the apparent natural cytotoxicity of normal peritoneal macrophages toward the murine MCA/76-9, MCA/76-45, and MCA/76-64 sarcoma cells in vitro, it was found that the peritoneal macrophages from nine different inbred strains of mice, as well as spleen and tumor-associated macrophages, preferentially lysed [125I]5-iodo-2'-deoxyuridine [( 125I]dUrd)-labeled target cells. However, unlabeled target cells were actively proliferating under the same conditions. Proliferation of target cells occurred independently of the lytic event, as measured by counting residual tumor cells at intervals or by pulsing cultures with tritiated thymidine [( 3H]dThd), both of which parameters were relatively the same in the presence or absence of macrophages. Moreover, macrophage-enhanced lysis of [125I]dUrd-labeled cells was not confined to tumor cells since adherent labeled nontransformed C57BL/6J 3T3 cells, mouse embryo fibroblasts, and suspended concanavalin A-stimulated lymphoblasts were also induced to release 125I faster in the presence than in the absence of macrophages. Prelabeled L1210 lymphoma cells were not lysed by normal macrophages. Lipopolysaccharide (LPS) treatment of resident peritoneal macrophages did not induce a stronger lytic effect than that induced by untreated macrophages, but it did result in macrophage-mediated inhibition of DNA synthesis by tumor cells. LPS-treated thioglycollate-elicited macrophages induced a higher specific 125I release from tumor cells than the release from untreated macrophages. Tumor target cells prelabeled with the less radiotoxic [131I]dUrd were also more predisposed to the lytic action of normal macrophages, while [3H]dThd-labeled target cells were relatively unaffected by the presence of macrophages. Thus certain types of normal and neoplastic cells may become highly susceptible to macrophages or their products after the target cell DNA had incorporated radioactive IdUrd.