Long-term self-maintenance of hemopoietic precursors in bone marrow culture derived from tumor necrosis factor-deficient mice is not a result of neoplastic transformation.

Abstract

In long-term bone marrow cultures derived from tumor necrosis factor-deficient mice the total cell production and the total duration of hemopoiesis are increased (the latter is comparable with mouse life span). Telomerase activity in cells of nonadherent fraction of long-term bone marrow cultures from tumor necrosis factor-deficient mice increases with time and peaks after 1-year culturing. Karyotyping of nonadherent and adherent cells of long-term bone marrow cultures revealed instability of nonadherent cells and hyperploidy of the stromal sublayer cells, which attested to the presence of a neoplastic transformation. However, cell differentiation is not blocked in long-term bone marrow cultures. The nonadherent fraction of long-term bone marrow cultures from tumor necrosis factor-deficient mice cannot be cultured without exogenous growth factors; in the presence of growth factors the cells proliferate, but cannot be passaged; stromal sublayer cells cannot be passaged as well. Intraperitoneal and intravenous injections of nonadherent cells to recipients with normal and radiation-attenuated immunity induced no tumor growth. Hence, peculiar dynamics of long-term bone marrow cultures from tumor necrosis factor-deficient mice cannot be explained by neoplastic transformation.