In order to clarify the mechanism of myelotoxicity of chloramphenicol (CP), the comparative studies were performed on CP induced colony growth inhibition of CFU-E, CFU-C and CFU-S in C57BL mice marrow cells in vitro and in vivo.
In vitro effect of CP: ⁵⁹Fe-incorporation into heme of reticulocytes was not affected by CP at 1000 μg/ml or less. Erythropoietin responsiveness of marrow cells was inhibited at 500 μg/ml. The colony growth of CFU-E and CFU-C was inhibited dose-dependently by CP, and 50% inhibition occurred at 17 μg/ml in CFU-E and 19 μg/ml in CFU-C respectively. The colony growth activity of marrow cells pretreated with CP was maintained better in CFU-S than CFU-E.
In vivo effect of CP: The colony growth of CFU-E, CFU-C and CFU-S in marrow cells from mice injected with CP (5 mg for 7 days) did not change, significantly compared to that of saline control mice as well as CFU-S in lethally irradiated recipient mice given the same dose of CP.
These results indicates that CP clearly exhibits a selective inhibition on the differentiation and proliferation of committed stem cell in vitro. However, the discrepancy of the action of CP in vitro and vivo raises an important problem. It might relate with the modifying host factors, but not relate the drug-metabolizing host ability because CFU-E colony growth inhibition was occurred by the addition of the serum from mice injected with CP.
These data of present work provide some evidence to the studies on the mechanism of myelotoxicity of CP.