Use of Human Lymphoblastoid Cells to Detect the Toxic Effect of Chloramphenicol and Metabolites Possibly Involved in Aplastic Anemia in Man

Abstract

Some Chloramphenicol (CAP) metabolites are suspected to be involved in the etiology of bone marrow aplasia in man. The objective of the present study was to investigate the cytotoxicity as well as the genotoxicity of CAP and six of its metabolites on human bone marrow cells (RiBM cells) and to compare these results with those obtained on human peripheral blood lymphocytes in order to estimate the relative sensitivity of the two types of cells. Three CAP metabolites NO-CAP, DH-CAP and NPAP inhibited 3H thymidine incorporation in RiBM cells at concentrations ranging from 2.10(-5) M to 2.10(-4) M. NO-CAP appeared as the most potent cytotoxic compound. CAP itself and NAPD presented some toxic effect at high concentration (1-2.10(-3) M). CAPG and HAP did not present any cytotoxic effect. By comparison, the response of human lymphocytes to CAP and its metabolites showed a similar pattern but DH-CAP was the most inhibitory compound. Concerning the genotoxic potential, NO-CAP and DH-CAP induced DNA single strand breaks in RiBM cells at concentrations of 1 and 2.10(-4) M with a dose response relationship. CAP and other metabolites were completely devoid of genotoxicity up to 4.10(-3) M. The results clearly showed that RiBM cells were much less susceptible to the genotoxic effect of CAP metabolites than human lymphocytes.