DNA damage induced by chloramphenicol and its nitroso derivative: damage in intact cells. 1987

A A Yunis, and G K Arimura, and M Isildar

We have postulated that the p-NO2 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-NO2 group, was without effect.

UI MeSH Term Description Entries
D009603 Nitroso Compounds Organic compounds containing the nitroso (-N Compounds, Nitroso
D009994 Osmolar Concentration The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Ionic Strength,Osmolality,Osmolarity,Concentration, Osmolar,Concentrations, Osmolar,Ionic Strengths,Osmolalities,Osmolar Concentrations,Osmolarities,Strength, Ionic,Strengths, Ionic
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002701 Chloramphenicol An antibiotic first isolated from cultures of Streptomyces venequelae in 1947 but now produced synthetically. It has a relatively simple structure and was the first broad-spectrum antibiotic to be discovered. It acts by interfering with bacterial protein synthesis and is mainly bacteriostatic. (From Martindale, The Extra Pharmacopoeia, 29th ed, p106) Cloranfenicol,Kloramfenikol,Levomycetin,Amphenicol,Amphenicols,Chlornitromycin,Chlorocid,Chloromycetin,Detreomycin,Ophthochlor,Syntomycin
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013438 Sulfhydryl Compounds Compounds containing the -SH radical. Mercaptan,Mercapto Compounds,Sulfhydryl Compound,Thiol,Thiols,Mercaptans,Compound, Sulfhydryl,Compounds, Mercapto,Compounds, Sulfhydryl
D013839 Thiamphenicol A methylsulfonyl analog of CHLORAMPHENICOL. It is an antibiotic and immunosuppressive agent. Dextrosulfenidol,Thiophenicol,Raceophenidol,Thiamcol,Thiomycetin,Urfamycin,Vicemycetin

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