Effects of tumor bearing on the dynamics of host hemopoietic cells.

Hemopoietic status of the host is an important consideration in any cancer chemotherapy protocol. This paper examines several aspects of the response of the host lymphomyeloid system to tumors transplanted elsewhere: (a) characteristics of host leukocytes migrating into the tumor; (b) leukocyte dynamics in the marrow and the spleen; and (c) dynamics of hemopoietic stem cells. Repeated prelabeling of mice with 3HTdR prior to Ehrlich ascites tumor (EAT) transplantation indicated a large-scale, selective migration and/or retention of newly formed lymphocytes and monocytes within the tumor. Similar observations were also made in sc transplants of strain-specific TA-3(St) tumor. Bone marrow was found to be a major source of these mononuclear cells since their accumulation was suppressed by a prior irradiation of host marrow. Labeling with 125I-antimouse IgM, with or without prior incubation of cells with anti-theta serum, revealed that, within the 7-day-old EAT, about a third of the small lymphocytes were maturing B cells having readily detectable surface IgM, about a third were T cells expressing theta antigen, and the rest had neither marker, possible including very immature B cells. A high incidence of last cell category was also found in subcutaneous TA-3(St) tumors. Ip transplantation of 10(6) EAT cells into CBA/HT6 or TA-3(St) cells into A/J mice caused a transient decline in femoral marrow leukocyte level (affecting lymphocytes most) followed by a recovery and an overshoot. In contrast, there was a steady rise in splenic weight or cellularity mostly accountable for by lymphocytes. This was partly due to local lymphoid proliferation and partly due to extraneous migration. Parabiosis of CBA with T6 chromosome-bearing CBA/HT6 mice revealed that a large proportion of cells dividing in the spleen of the CBA host after tumor transplantation had migrated recently from blood. Using partial marrow chimeras (repopulated with T6 chromosome-bearing marrow cells), bone marrow was identified as their major source. Furthermore, host spleens showed an increased incidence of small lymphocytes bearing no detectable surface-IgM nor theta antigen (possibly inclusive of immature B cells), and a low incidence of T cells. Tumor transplantation produced a rapid and substantial decline in the pleuripotent stem cell (CFU-S) content of the femoral marrow followed by a recovery. The converse was true for the CFU content of the spleen, and in addition, there was an initial rise in the blood CFU level, suggesting an early CFU traffic from marrow to spleen. A qualitatively similar pattern was also noted for stem cells committed to granulocyte or macrophage development as evaluated from in vitro colony assays. An early rise in splenic CFU level was also elicited by injecting sonicated tumor cells or their plasma membrane fractions, thus possibly indicating an antigen-driven effect. A high level of colony-stimulating activity (for in vitro colony growth) was found in the tumor fluid...