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DNA damage induced by chloramphenicol and its nitroso derivative: Damage in intact cells
Author(s) -
Yunis A. A.,
Arimura G. K.,
Isildar M.
Publication year - 1987
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830240110
Subject(s) - dna damage , chloramphenicol , dna , chemistry , in vitro , microbiology and biotechnology , biology , biochemistry , antibiotics
We have postulated that the p‐NO 2 group of chloramphenicol (CAP) is the structural feature underlying aplastic anemia from this drug. In a series of studies to examine this hypothesis we have demonstrated the toxic nature of the CAP‐reduction intermediate nitroso CAP (NO‐CAP) and its damaging effect on isolated DNA in vitro. The present study was designed to examine the comparative effects of CAP, NO‐CAP, and thiamphenicol (TAP) on the integrity of DNA in intact cells. By using the alkaline elution technique of Kohn, DNA damage in the form of single strand breaks could be readily demonstrated in cultured Raji cells and in PHA‐stimulated normal human lymphocytes by small concentrations of NO‐CAP (0.05‐0.1 mM). A small but reproducible effect was observed from large concentrations of CAP (2 mM). In contrast, TAP, lacking the p‐NO 2 group, was without effect.