Bleomycin, in Contrast to Gamma Irradiation, Induces Extreme Variation of DNA Strand Breakage from Cell to Cell

Östling, O.; Johanson, Karl J.

doi:10.1080/09553008714552201

Cited by 88 publications

(38 citation statements)

References 6 publications

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“…4). The comet assay has been used to analyze DNA breakage in mammalian cells (15,32) and is recognized as a research tool in the carcinogenesis, genotoxicity, radiotherapy, and environmental fields (33,34,35,36,37). Here, the cytotoxicity of colistin was extended to mammalian cells, specifically, Vero cells, which are a lineage isolated from monkey kidney epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect between Colistin and Bacteriocins in Controlling Gram-Negative Pathogens and Their Potential To Reduce Antibiotic Toxicity in Mammalian Epithelial Cells

Naghmouchi

Baah²,

Hober

et al. 2013

Antimicrob Agents Chemother

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e Pathogens resistant to most conventional antibiotics are a harbinger of the need to discover novel antimicrobials and anti-infective agents and develop innovative strategies to combat them. The aim of this study was to assess the in vitro activity of colistin alone or in combination with two bacteriocins, nisin A and pediocin PA-1/AcH, against Salmonella choleraesuis ATCC 14028, Pseudomonas aeruginosa ATCC 27853, Yersinia enterocolitica ATCC 9610, and Escherichia coli ATCC 35150 (O157:H7). The strain most sensitive to colistin was enterohemorrhagic E. coli O157:H7, which was inhibited at a concentration of about 0.12 g/ml. When nisin A (1.70 g/ml) or pediocin PA-1/AcH (1.56 g/ml) was combined with colistin, the concentrations required to inhibit E. coli O157:H7 were 0.01 and 0.03 g/ml, respectively. The in vitro antigenotoxic effect of colistin was determined by using the comet assay method to measure the level of DNA damage in freshly isolated human peripheral blood leukocytes (PBLs) incubated with colistin for 1 h at 37°C. Changes in the tail extents of PBLs of about 69.29 ؎ 0.08 m were observed at a final colistin concentration of about 550 ng/ml. Besides the synergistic effect, the combination of colistin (1 mg/ml) and nisin (2 mg/ ml) permitted us to re-evaluate the toxic effect of colistin on Vero (monkey kidney epithelial) cells.T he emergence of multidrug-resistant pathogenic bacteria highlights a matching need for new therapeutic options. Better management and reasonable use of antibiotics are imperatively required in order to reduce the rate of emergence of antibioticresistant strains. Currently, clinicians and microbiologists are being forced to re-evaluate the clinical use of colistin, a relatively old polypeptide antibiotic, because there appear to be no promising therapeutic agents in the drug development pipeline (1). Colistin became available for clinical use in the 1960s but was replaced in the 1970s with antibiotics considered less toxic. Nephrotoxicity and neurotoxicity were the major side effects that led to the discontinuation of the routine use of colistin (1, 2). Two forms of colistin are commercially available, colistin sulfate, which is for oral and topical use, and colistimethate sodium (sodium colistin methanesulfonate, colistin sulfomethate sodium), which is for parenteral use or inhalation. The structure of polymyxins consists of a cyclic decapeptide bound to a fatty acid (3). Colistin binds to the anionic part of the lipopolysaccharide (LPS), leading to deep disruption in the bacterial membrane, enhancing its permeability and causing cell lysis (4). A role for LPS as a major receptor of colistin was proposed (5), and the mode of action involved a hydrophobic interaction between the nine-carbon fatty acid side chain of colistin and the fatty acid portion of lipid A (6). Strains of Escherichia coli and Klebsiella pneumoniae have become increasingly resistant to expanded-spectrum cephalosporins (7) but remain globally sensitive to tigecycline and colistin (8). The use of polymyxins t...

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Section: Discussionmentioning

confidence: 99%

Synergistic Effect between Colistin and Bacteriocins in Controlling Gram-Negative Pathogens and Their Potential To Reduce Antibiotic Toxicity in Mammalian Epithelial Cells

Naghmouchi

Baah²,

Hober

et al. 2013

Antimicrob Agents Chemother

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“…Thus, lesions in cell surfaces and intracellular DNAs are unlikely to be equally distributed from cell to cell. Results of the current study provide a cellular and molecular basis for the recovery of low-and high-molecular-weight DNAs from mammalian cells after short incubations with bleomycins (4,13,17).…”

Section: Methodsmentioning

confidence: 99%

Lesions and preferential initial localization of [S-methyl-3H]bleomycin A2 on Saccharomyces cerevisiae cell walls and membranes

Moore

Valle

McKoy

et al. 1992

Antimicrob Agents Chemother

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Extensive lesions were produced in cell walls of Saccharomyces cerevisiae by the bleomycin family of anticancer antibiotics (30 min to 4 h). Electron micrographs revealed that the alterations were most frequently large breaks and small interruptions or holes in cell walls, which sometimes extended into cell membranes. Large portions of cell walls were sometimes lost. Cell walls were frequently ruptured in one or more positions. More than 75% of bud scar regions in single-plane sections and all bud scars in serial sections exhibited many interruptions and breaks after 3 or 4 h of treatment. The discovery of extensive damage to cell walls was consistent with the preferential (approximately 70%) association of radiolabeled bleomycin with cell walls and perimeters of bud scar regions after short exposures (30 min). After longer exposures, the distribution of silver grains changed from a predominant association with cell walls (30 min) to an increased association with the cell cytoplasm (1 to 4 h). This correlated with increased ultrastructural damage, since damage to cell walls was generally more frequent and more severe with increasing length of treatment (30 min to 4 h) or dose (25 to 100 micrograms/ml). Although DNA lesions are believed to be the lethal properties of bleomycins, the lesions produced in cell walls are also lethal properties of the antibiotics. The distributions of lesions on cell walls suggested a generalized interaction of the antibiotic with a cell wall component. These results led us to hypothesize a mechanism of effective antifungal action for the bleomycin family of antibiotics.

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“…Due to the low operating cost, it is a test used in the analysis of genotoxicity (Fairbairn et al 1995, McKelvey Martin et al 1993. It has some advantages over biochemical and cytogenetic tests, as it can be used for any cell type (any material that can be extracted from nucleated cells), requiring only a small number of them and do not require dividing cells (Ostling & Johanson 1987). As it was demonstrated in the present study, that cells in the control group displayed comets Level II.…”

Section: Discussionmentioning

confidence: 52%

Comparative Study of the Clastogenic Action of Bovine Herpesvirus 1 (Bohv-1) in Primary and Established Cell Cultures

Rocha¹,

Belloti²,

Pavão³

et al. 2010

VR&R

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The concern about the transmission of infectious diseases by the use of biotechnologies, like in vitro fertilization (IVF), has been increasing. The aim of this study was to verify the clastogenic alterations in the DNA of Madin-Darby Bovine Kidney (MDBK) and Bovine Oviduct Epithelial Cells (BOEC) infected or not with bovine herpesvirus 1 (BoHV-1), for 24 hours, by the use of the Comet Assay or SingleCell Gel Electrophoresis (SCGE). The nuclear change was evaluated by measuring the extent of DNA damage, where it was possible to observe 1.7% of level II comet and 2.1% of level IV in the BOEC group "in situ". However, in BOEC infected by the virus the damages observed were 13.8% comet level I, 0.6% level III and 1.2% level IV. The MDBK cells not infected group showed displayed 1.9% level II and the infected group 26 % level I, 12.3 % level II and 6.1 % level III. All groups, regardless if they were infected or not by the virus, were considered positive by the comet assay, maybe because there has not been virus association with the cell DNA. The number of comets detected in the BOEC "in situ" corresponds to spontaneous mutations that use to be present in organisms with failure of DNA repair. In vitro established and primary cells show greater failure frequency in DNA repair mechanisms, and may present more mutations. Therefore, in vitro models provide better conditions to mimic in vivo conditions. These data have demonstrated that not always the IVF problems are due to pathogens infection.

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Bleomycin, in Contrast to Gamma Irradiation, Induces Extreme Variation of DNA Strand Breakage from Cell to Cell

Cited by 88 publications

References 6 publications

Synergistic Effect between Colistin and Bacteriocins in Controlling Gram-Negative Pathogens and Their Potential To Reduce Antibiotic Toxicity in Mammalian Epithelial Cells

Synergistic Effect between Colistin and Bacteriocins in Controlling Gram-Negative Pathogens and Their Potential To Reduce Antibiotic Toxicity in Mammalian Epithelial Cells

Lesions and preferential initial localization of [S-methyl-3H]bleomycin A2 on Saccharomyces cerevisiae cell walls and membranes

Comparative Study of the Clastogenic Action of Bovine Herpesvirus 1 (Bohv-1) in Primary and Established Cell Cultures

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