USE OF HUMAN LYMPHOBLASTOID-CELLS TO DETECT THE TOXIC EFFECT OF CHLORAMPHENICOL AND METABOLITES POSSIBLY INVOLVED IN APLASTIC-ANEMIA IN MAN

Some Chloramphenicol ( CAP) metabolites are suspected to be involved i n the etiology of bone marrow aplasia in man. The objective of the pre sent study was to investigate the cytotoxicity as well as the genotoxi city of CAP and six of its metabolites on human bone marrow cells (RiB M cells) and to compare these results with those obtained on human per ipheral blood lymphocytes in order to estimate the relative sensitivit y of the two types of I:ells. Three CAP metabolites NO-CAP, DH-CAP and NPAP inhibited 3H thymidine incorporation in RiBM cells at concentrat ions ranging from 2.10(-5)M to 2.10(-4)M. NO-CAP appeared as the most potent cytotoxic compound. CAP itself and NAPU presented some toxic ef fect 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 th e most inhibitory compound. Concerning the genotoxic potential, NO-CAP and DH-CAP induced DNA single strand breaks in RiBM cells at concentr ations of 1 and 2.10(-4)M with a dose response relationship. CAP and o ther metabolites were completely devoid of genotoxicity up to 4.10(-3) M. The results clearly showed that RiBM cells were much less susceptib le to the genotoxic effect of CAP metabolites than human lymphocytes.