AKR murine leukemia viruses and long-term bone marrow cultures from AKR and SJL mice

We have evaluated the effects of AKR mouse retroviruses on a system of long-term bone marrow cultures which allows prolonged replication of hemopoietic stem cells (CFUs) and granulocyte-monocyte progenitors with production of mature granulocytes. Ecotropic-nononcogenic virus is expressed in all cultures and does not adversely effect stem cell replication. We found, however, that cultures established from mice treated in vivo with lymphomagenic AKR viruses (Gross murine leukemia virus and AKR SL3 murine leukemia virus) showed a more rapid decline in CFUs and CFUc than cultures from "normal" AKR mice. Only the former cultures were found to produce lymphomagenic viruses. Furthermore, it was shown that addition of lymphomagenic virus to three-week marrow cultures established from AKR and SJL mice also caused a prompt decline in progenitor cell production and granulopoiesis when compared to medium-treated control cultures. The fate of all cultures was a loss of CFUc and granulocytes with a continuous production of macrophages. The change to macrophage production occurred earlier in the cultures treated with lymphomagenic virus or in those derived from lymphomagenic virus-treated animals. A study of these bone marrow-drived macrophage cultures, as well as cultures of similar morphology but of thymic origin, showed that they could be maintained as continuous lines. Cells from three of the cultures from lymphomagenic virus-treated animals plroduced locally growing sarcoma when inoculated into mice. The macrophages from the declined marrow cultures differed in certain properties from those of the established lines.