title: DNA damage in intact cells induced by bacterial metabolites of chloramphenicol.
abstract: Four chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria were examined with respect to their capacity to induce DNA damage in intact cells. The induction of DNA single-strand breaks in Raji cells, activated human lymphocytes, and human marrow cells was assayed by the alkaline elution technique. One of the four compounds tested, dehydro-CAP, was capable of inducing DNA single-strand breaks in all three cell systems at concentrations of 10(-4) M. This effect is comparable to that observed previously with nitroso-CAP, the nitroreduction intermediate of CAP. The nitroreduction of dehydro-CAP by human bone marrow cell homogenate was detected by the production of the corresponding amino derivative amounting to 5.6 X 10(-5) M from 2 X 10(-3) M substrate under aerobic conditions. In sharp contrast, nitroreduction of CAP by bone marrow could not be demonstrated. The genotoxicity of dehydro-CAP, its relative stability compared to the nitroso-CAP, and its nitroreducibility by bone marrow suggest that this bacterial metabolite of CAP may play a key role as a mediator of aplastic anemia in the predisposed host.
authors: Department of Medicine, University of Miami School of Medicine, FL 33101.
authors: M
authors: M
authors: Isildar
authors: J J
authors: JJ
authors: Jimenez
authors: G K
authors: GK
authors: Arimura
authors: A A
authors: AA
authors: Yunis
mesh_terms: D001853:Bone Marrow / Q000032:analysis / Q000187:drug effects; D002460:Cell Line; D002701:Chloramphenicol / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D004247:DNA / Q000302:isolation & purification; D004249:DNA Damage; D004755:Enterobacteriaceae / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000032:analysis / Q000187:drug effects; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D002701:Chloramphenicol; C026099:nitrosochloramphenicol; D004247:DNA; D009247:NADH, NADPH Oxidoreductases