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Cytotoxicity and DNA damaging potency of chloramphenicol and six metabolites: a new evaluation in human lymphocytes
C Lafarge-Frayssinet1, S Robbana-Barnat, C Frayssinet
1Laboratory of Molecular Genetics, UPR 42 CNRS, Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
Abstract:
Chloramphenicol (CAP) is an antibiotic which has been implicated in the etiology of aplastic anemia in man. This product is also used in veterinary medicine. The medical use of chloramphenicol has been limited to cases where the drug is indispensible but veterinary use may lead to the presence of residues in the meat of treated animals and it is essential to establish acceptable levels of intake of such residues in order to protect human health. CAP is metabolized into at least 6 metabolites: nitroso-CAP (NO-CAP), formed in the liver, 3 excretion products: the glucuronide (CAP-G), the CAP base (NAPD), and an alcoholic derivative, HAP. Dehydro-CAP (DH-CAP) and the dehydro-CAP base (NPAP) are formed by enterobacteria in the large bowel. The objective of the present study was to investigate (1) the cytotoxicity of CAP and its metabolites and (2) their ability to induce DNA damage in human cells. This work was performed with human peripheral blood lymphocytes (PBL) and with a lymphoma cell line (Raji).