Chloramphenicol damages bacterial DNA

Jackson, Suzanne F.; Wentzell, Byron R.; McCalla, D. R.; Freeman, Karl B.

doi:10.1016/0006-291x(77)91233-5

Cited by 14 publications

(5 citation statements)

References 12 publications

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“…When CAP is added to a culture of uniformly labeled cells growing exponentially at the permissive temperature, it usually results in a 30 to 60% increase in acid-precipitable counts before incorporation ceases. It has been generally interpreted that this incorporation represents the completion of the round of DNA synthesis which was in progress and that reinitiation of replication is dependent upon subsequent protein synthesis (7,13,14). When temperature-sensitive DNA initiation mutants are placed at nonpermissive temperatures, there is also an approximate 30 to 60% increase in acid-precipitable counts, which has also been interpreted as representing completion of the ongoing round of DNA synthesis.…”

Section: Resultsmentioning

confidence: 99%

Effect of blocking protein synthesis at nonpermissive temperatures on temperature-sensitive deoxyribonucleic acid mutants of Escherichia coli

Evans¹,

Forrest²,

Lawrence³

et al. 1979

J Bacteriol

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When protein synthesis was blocked in temperature-sensitive deoxyribonucleic acid synthesis mutants of Escherichia coli at nonpermissive temperatures, it reduced the amount of apparent subsequent chain elongation to approximately half that observed in the mutants either at nonpermissive temperatures alone or when protein synthesis was blocked at the permissive temperature. Blocking protein synthesis at the nonpermissive temperatures for periods of 40 min caused the loss of ability to reinitiate deoxyribonucleic acid synthesis at the permissive temperature.

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Section: Resultsmentioning

confidence: 99%

Effect of blocking protein synthesis at nonpermissive temperatures on temperature-sensitive deoxyribonucleic acid mutants of Escherichia coli

Evans¹,

Forrest²,

Lawrence³

et al. 1979

J Bacteriol

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“…McCann et al (1976) and Jackson et al (1977) found that the toxicity of chloramphenicol interfered with attempts to examine the mutagenicity of this drug in S. Typhimurium. In E. coli B/r and S. Typhimurium strains, Jackson et al (1977) tested mutagenicity of two chloramphenicol isomers: D-threo-chloramphenicol known to inhibit protein synthesis and L-threo-chloramphenicol that does not inhibit protein synthesis. The L-threo-chloramphenicol that was not toxic to bacteria induced reverse mutations in S. Typhimurium TA100 and TA1535 without metabolic activation, while the mutagenicity of D-threo-chloramphenicol was masked by its toxicity.…”

Section: Genotoxicitymentioning

confidence: 99%

“…However, some controversial outcomes suggesting the possibility of DNA damage induced by chloramphenicol in E. coli and in S. Typhimurium have been published by McCann et al (1976), Jackson et al (1977), Mitchell et al (1980) and Suter and Jaeger (1982). McCann et al (1976) and Jackson et al (1977) found that the toxicity of chloramphenicol interfered with attempts to examine the mutagenicity of this drug in S. Typhimurium. In E. coli B/r and S. Typhimurium strains, Jackson et al (1977) tested mutagenicity of two chloramphenicol isomers: D-threo-chloramphenicol known to inhibit protein synthesis and L-threo-chloramphenicol that does not inhibit protein synthesis.…”

Section: Genotoxic Effects Of Chloramphenicol In Prokaryotic and In Lmentioning

confidence: 99%

Scientific Opinion on Chloramphenicol in food and feed

2014

EFS2

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Chloramphenicol is an antibiotic not authorised for use in food-producing animals in the European Union (EU). However, being produced by soil bacteria, it may occur in plants. The European Commission asked EFSA for a scientific opinion on the risks to human and animal health related to the presence of chloramphenicol in food and feed and whether a reference point for action (RPA) of 0.3 µg/kg is adequate to protect public and animal health. Data on occurrence of chloramphenicol in food extracted from the national residue monitoring plan results and from the Rapid Alert System for Food and Feed (RASFF) were too limited to carry out a reliable human dietary exposure assessment. Instead, human dietary exposure was calculated for a scenario in which chloramphenicol is present at 0.3 µg/kg in all foods of animal origin, foods containing enzyme preparations and foods which may be contaminated naturally. The mean chronic dietary exposure for this worst-case scenario would range from 11 to 17 and 2.2 to 4.0 ng/kg b.w. per day for toddlers and adults, respectively. The potential dietary exposure of livestock to chloramphenicol was estimated to be below 1 µg/kg b.w. per day. Chloramphenicol is implicated in the generation of aplastic anaemia in humans and causes reproductive/hepatotoxic effects in animals. Margins of exposure for these effects were calculated at 2.4 × 10 5 or greater and the CONTAM Panel concluded that it is unlikely that exposure to food contaminated with chloramphenicol at or below 0.3 µg/kg is a health concern for aplastic anaemia or reproductive/hepatotoxic effects. Chloramphenicol exhibits genotoxicity but, owing to the lack of data, the risk of carcinogenicity cannot be assessed. The SUMMARYChloramphenicol is a broad-spectrum antibiotic effective against Gram-positive and Gram-negative bacteria and, in the past, has been widely used to treat infections in both humans and animals. Chloramphenicol is not authorised for use in food-producing animals in the European Union (EU) but may be used in human medicine and in treatments for non-food-producing animals. Apart from its potential occurrence as a residue in food from illicit treatment of food-producing animals, chloramphenicol has also been used in feed and food enzyme products and may occur naturally in plants from its production by the soil bacterium Streptomyces venezuelae.The EFSA Scientific Opinion entitled "Guidance on methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances present in food of animal origin" identified an approach for establishing RPAs for various categories of non-allowed pharmacologically active substances. However, the opinion also identified certain categories of non-allowed pharmacologically active substances that are considered to be outside the scope of the procedure, including substances causing blood dyscrasias (aplastic anaemia) such as chloramphenicol. As chloramphenicol is excluded fro...

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“…That the induction of DNA damage is related to nitroreduction is also suggested by other investigations. For example, CAP, which is readily reduced by bacteria, is mutagenic in the Ames salmonella/microsome bioassay system [23], which is an indicator of DNA damage. CAP also induces DNA strand breaks in E. coli and S. typhimurium under aerobic conditions [23].…”

Section: Poimentioning

confidence: 99%

“…For example, CAP, which is readily reduced by bacteria, is mutagenic in the Ames salmonella/microsome bioassay system [23], which is an indicator of DNA damage. CAP also induces DNA strand breaks in E. coli and S. typhimurium under aerobic conditions [23]. Furthermore, CAP produced damage in isolated DNA during its electrochemical reduction [24-261.…”

Section: Poimentioning

confidence: 99%

DNA damage in intact cells induced by bacterial metabolites of chloramphenicol

et al. 1988

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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.

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Chloramphenicol damages bacterial DNA

Cited by 14 publications

References 12 publications

Effect of blocking protein synthesis at nonpermissive temperatures on temperature-sensitive deoxyribonucleic acid mutants of Escherichia coli

Effect of blocking protein synthesis at nonpermissive temperatures on temperature-sensitive deoxyribonucleic acid mutants of Escherichia coli

Scientific Opinion on Chloramphenicol in food and feed

DNA damage in intact cells induced by bacterial metabolites of chloramphenicol

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