摘要：

Lewis lung carcinoma (LLC) of C57BL/6 mice, a transplantable tumor widely metastatic by 6–7 days post implant (PI), caused hematopoietic alterations such as progressive anemia (hemoglobin: day 1 PI, 11.0 g/dl; day 19 PI, 7.8 g/dl), neutrophilia (neutrophils: day 1 PI, 2 × 10³/µl; day 19 PI, 22 × 10³/µl), and marrow and splenic myeloid hyperplasia (marrow myeloid-to-erythroid ratio: day 1 PI, 1:1; day 7 PI, 3:1). Accompanying these changes were an increased concentration of marrow granulocyte-macrophage colony-forming units (culture) (GM-CFU_c) (day 3 PI, LLC 185±27% of control; day 19 PI, LLC 265±10% of control) and accelerated cycling of these myeloid progenitors [day 3 PI, LLC 45.3±6.5% GM-CFU_c in cycle vs, sham (media) injected 17.5±10.5%; day 7 PI, LLC 52.2±2.5% vs. sham (media) injected 29.8±9.8%; day 11 PI, LLC 56.2±4.4% vs. sham (media) injected 22.2±14%]. This study questioned whether enhanced hematopoiesis was a result of progressive tumor growth or whether the injection of tumor cells could evoke the response. By use of groups of C57BL/6 mice given an injection of live LLC cells, x-irradiated killed LLC cells, or media, the hematopoietic response to live LLC cells versus dead LLC cells could be dissected. A biphasic colony-stimulating activity (CSA) response in the sera of tumor bearers was found to account for the myelopoietic changes. The first wave of CSA from days 1 to 3 PI stimulated 168±3.7% more GM-CFU_c than control sera and was likely released by dead cells of the tumor inoculum; the second wave from day 7 onward stimulated 220±7.6% more colonies and was a result of the enlarging tumor mass. Tumor growth was necessary for GM-CFU_c proliferation, and the declining growth fraction at day 19 in LLC-bearing mice suggested that hematopoietic exhaustion was a consequence of tumor growth.

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