The cellular uptake and covalent binding of nitroso-chloramphenicol.
A comparative study of the cellular transport of CAP and its nitroso derivative (NO-CAP) was carried out in Raji cells, a transformed human lymphoblastoid cell line. Both agents were concentrated by the cells by a factor of 3 (cellular/extracellular concentration ratio). The cellular uptake of NO-CAP, like that of CAP, was found to be rapid and temperature-independent. Thus the greater cytotoxicity of NO-CAP is apparently not due to an enhanced uptake of the nitroso derivative relative to CAP. In contrast to the similarity of uptake, NO-CAP becomes covalently bound to both Raji cells and freshly isolated human bone marrow cells to a much higher extent (15-fold). Also, cells previously loaded with CAP or NO-CAP retain three times as much of the nitroso compound during a 24 hr dialysis against a drug-free isotonic solution. The increased binding of NO-CAP to human hematopoietic cells attests to the greater reactivity of the p-substituted aromatic nitroso group and is consistent with the postulate that reduction products of the nitro group of CAP may be responsible for CAP-induced aplastic anemia.
D000741:Anemia, Aplastic / Q000139:chemically induced; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D002051:Burkitt Lymphoma; D002460:Cell Line; D002701:Chloramphenicol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D003956:Dialysis; D006801:Humans; D014316:Tritium
D014316:Tritium; D002701:Chloramphenicol; C026099:nitrosochloramphenicol