NITROSO-CHLORAMPHENICOL - POSSIBLE MEDIATOR IN CHLORAMPHENICOL-INDUCED APLASTIC-ANEMIA

  • 1 January 1980
    • journal article
    • research article
    • Vol. 96  (1) , 36-46
Abstract
The effects of CAP [chloramphenicol] and its nitroso derivative on DNA synthesis, CFU-C [in vitro myeloid colony-forming cell] growth, and cell viability in human bone marrow and on mouse CFU-S [pluripotential hematopoietic stem cell] viability were compared in vitro. As previously reported, CAP inhibited DNA synthesis only when used in high concentrations (> 3 .times. 10-4 M), and the inhibition was largely reversible. It also caused a reversible concentration-dependent inhibition of CFU-C growth but did not affect marrow cell viability. In sharp contrast, nitroso-CAP inhibited DNA synthesis in much lower concentrations, and caused irreversible inhibition of CFU-C growth and cell death at 5 .times. 10-5 M, and irreversible mouse CFU-S damage. In a rapidly growing human lymphoid cell line, nitroso-CAP caused accumulation of cells in the G2M phase, and increasing cell death within the arrested population. CAP-induced aplastic anemia evidently occurs in the predisposed host who provides the milieu for the transformation of the p-NO2 group of the drug to toxic intermediates.