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.
Botryodiplodin, a mycotoxin synthesized by some strains of Penicillium roqueforti was tested for lethal and mutagenic effects on Salmonella typhimurium (TA98). Botryodiplodin was active in the histidine reversion system without metabolic activation.
Two strains of white rats, one of which (Sprague‐Dawley) was sensitive, another (Wistar) not, to liver cancerization by DAB, were studied comparatively in an attempt to find biochemical characteristics which might explain this difference, that is changes in the activity of the enzyme, DAB‐reductase, and in the binding of azo metabolites to liver proteins.
The animals were administered a whole diet, rich in proteins and in vitamins. When not fed DAB, the activity of DAB‐reductase was five‐fold higher in Wistar than in Sprague‐Dawley rats; the continuous administration of DAB causes a progressive decrease of the enzyme activity in the two strains. After 10 days of carcinogenic diet the amounts of azo proteins are maximal and at this time they are twice higher in Sprague‐Dawley than in the Wistar rats. Hepatomas appear in the Sprague‐Dawley strain without a lag phase, as early as the fifth week of treatment.
The resistance to cancerization appears to depend principally on a genetic factor which would allow a more or less efficient detoxification, mediated by the enzyme, DAB‐reductase.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.