EFFECT OF INVIVO ADMINISTRATION OF CISPLATIN ON THE COLONY-FORMING ABILITY OF MURINE BONE-MARROW CELLS

In vitro colony forming ability of bone marrow cells obtained from cisplatin-treated C3H/He mice was studied. Mice were administered cisplatin in a single intraperitoneal dose of 10 mg/kg body wt, 24 h prior to the harvest of femoral bone marrow cells. Incubation of untreated bone marrow cells without any CSF in vitro showed little colony forming ability which was marginally enhanced in cisplatin-treated bone marrow cells. Presence of M-CSF (250 U/ml) or GM-CSF (250 U/ml) in the culture medium significantly augmented the colony forming ability of both untreated and cisplatin-treated bone marrow cells. In the presence of M-CSF, colony forming units - macrophage (CFU-M) were predominantly high in untreated bone marrow cells, followed with CFU - granulocyte - macrophage (CFU-GM). The number of CFU-M was significantly up-regulated in response to M-CSF in bone marrow cells obtained from cisplatin administered mice, whereas the number of CFU-GM remained unchanged, as compared to untreated mice. Both CFU-M and CFU-GM were enhanced in the presence of GM-CSF in untreated bone marrow cells. Cisplatin-treated bone marrow cells on incubation in the presence of GM-CSF showed a significant enhancement of CFU-M and GM as compared to untreated samples. IL-1 (100 U/ml) in the presence of M-CSF significantly up-regulated colony forming ability of cisplatin-treated bone marrow cells, whereas TNF (100 U/ml) inhibited the colony forming ability. These effects of IL-1 and TNF on the in vitro colony formation of cisplatin-treated bone marrow cells were reversed in the presence of anti-IL-1 and anti-TNF antibodies, respectively.