Influence of novobiocin on &lt;FONT FACE=Symbol&gt;g&lt;/font&gt;-irradiation G0-lymphocytes as analyzed by cytogenetic endpoints

Savoldi-Barbosa, Marcela; Sakamoto-Hojo, Elza T.; Takahashi, Catarina Satie

doi:10.1590/s1415-47571999000200014

Cited by 3 publications

(4 citation statements)

References 30 publications

(31 reference statements)

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“…It is a non-specific inhibitor of DNA topoisomerase II (DNA topoII), which may trigger a positive TGx-DDI signal at higher concentrations, as seen with the 250 μM concentration. Thus, our results indicate that this compound may be weakly DDI; the weak response may be due to a difference in the binding constant for topoII compared to other bacterial gyrase inhibitors (Savoldi-Barbosa et al, 1999). Indeed, two other bacterial gyrase inhibitors with topoII inhibitory activity (i.e., ciprofloxacin and norfloxacin) that were previously tested using the TGx-DDI biomarker yielded conflicting results with respect to classification.…”

Section: Discussionmentioning

confidence: 76%

“…NOV was also widely used as a human therapeutic (Committee for Veterinary Medicinal Products, 1999). NOV interacts directly with the B subunit (GyrB) of the bacterial DNA gyrase enzyme (Maxwell, 1993;Heide, 2009a) and it is a non-specific inhibitor of DNA topoisomerase II (DNA topoII) enzyme (Savoldi-Barbosa et al, 1999). NOV has been shown to cause concentration-dependent DNA fragmentation that preceded apoptosis in primary cultures of mouse thymocytes, by inhibiting DNA-rejoining activity of the enzyme (Onishi et al, 1993).…”

Section: Case Study Chemical Selection and Rationalementioning

confidence: 99%

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Integrated Genotoxicity Testing of three anti-infective drugs using the TGx-DDI transcriptomic biomarker and high-throughput CometChip® assay in TK6 cells

et al. 2022

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Genotoxicity testing relies on the detection of gene mutations and chromosome damage and has been used in the genetic safety assessment of drugs and chemicals for decades. However, the results of standard genotoxicity tests are often difficult to interpret due to lack of mode of action information. The TGx-DDI transcriptomic biomarker provides mechanistic information on the DNA damage-inducing (DDI) capability of chemicals to aid in the interpretation of positive in vitro genotoxicity data. The CometChip® assay was developed to assess DNA strand breaks in a higher-throughput format. We paired the TGx-DDI biomarker with the CometChip® assay in TK6 cells to evaluate three model agents: nitrofurantoin (NIT), metronidazole (MTZ), and novobiocin (NOV). TGx-DDI was analyzed by two independent labs and technologies (nCounter® and TempO-Seq®). Although these anti-infective drugs are, or have been, used in human and/or veterinary medicine, the standard genotoxicity testing battery showed significant genetic safety findings. Specifically, NIT is a mutagen and causes chromosome damage, and MTZ and NOV cause chromosome damage in conventional in vitro tests. Herein, the TGx-DDI biomarker classified NIT and MTZ as non-DDI at all concentrations tested, suggesting that NIT’s mutagenic activity is bacterial specific and that the observed chromosome damage by MTZ might be a consequence of in vitro test conditions. In contrast, NOV was classified as DDI at the second highest concentration tested, which is in line with the fact that NOV is a bacterial DNA-gyrase inhibitor that also affects topoisomerase II at high concentrations. The lack of DNA damage for NIT and MTZ was confirmed by the CometChip® results, which were negative for all three drugs except at overtly cytotoxic concentrations. This case study demonstrates the utility of combining the TGx-DDI biomarker and CometChip® to resolve conflicting genotoxicity data and provides further validation to support the reproducibility of the biomarker.

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Section: Discussionmentioning

confidence: 76%

Section: Case Study Chemical Selection and Rationalementioning

confidence: 99%

Integrated Genotoxicity Testing of three anti-infective drugs using the TGx-DDI transcriptomic biomarker and high-throughput CometChip® assay in TK6 cells

et al. 2022

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“…PHA selectively stimulates T-lymphocytes to enter mitosis. The widespread popularity of peripheral blood culture as means of chromosome analysis has been largely dependent on that mitogen (Boerrigter and Vijg, 1992, Maluish and Strong, 1986and Savoldi-Barbosa et al, 1999. It is well established that unstable aberrations like dicentric chromosomes, chromosome breaks and acentric fragments can be eliminated during the cell division.…”

mentioning

confidence: 99%

The Effect of Phytohaemagglutinin and Colcemid on the Reliability of the Chromosome Aberration Analysis after Ionizing Radiation Exposure

2011

Egypt. J. Rad.Sci.

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HERE are some correlations between cell's ability to remove DNA damage and proliferative activity. Another phenomenon was observed that the frequency of radiationinduced aberration can be influenced according to the concentrations of colcemid or colchicine which used for arresting the cell cycle in metaphase. The aim of this study is to improve the technical accuracy of the chromosome aberration analysis and demonstrate the dose-dependent effect of colcemid and colchicine which may be of interest to physicians encountering irradiated patients. So, the study examined the effect of phytohaemagglutinin (PHA) and colcemid or colchicine dose concentrations on DNA repair capacity and chromosome aberration yields in human blood lymphocytes exposed to ionizing radiation. Whole blood samples were irradiated with (2 Gy) γ-rays. PHA (0.2 ml) was added to blood cultures either immediately after irradiation or after a certain recovery period (1 & 2 h). In the second part of the experiment, we used both colcemid and colchicine with 2 different concentrations (0.025 & 0.05 μg/ ml). The number of dicentric chromosomes and acentric fragments were significantly increased in lymphocytes stimulated by PHA immediately after the irradiation. On the other hand, the use of colcemid with dose range 0.025 to 0.5 μg/ ml is better than colchicine with the same doses in the accurate estimation of the absorbed radiation dose.

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“…Several studies have shown that the administration of vitamins, fatty acids and their constituents, chlorophyllin salt and other substances resulted in a protective effect against the chromosomal damage induced by radiation or by chemical agents in the somatic and germ cells of rodents (Khan and Sinha 1996, Antunes and Takahashi 1998, Savoldi-Barbosa et al 1999, Bez et al 2001, Rampazo et al 2002.…”

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confidence: 99%

Standardized Solanum melongena Extract Presents Protective Effects against Chromosomal Aberrations Induced by Doxorubicin in Wistar Rat Bone Marrow Cells

2003

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Doxorubicin (DXR) is a potent antitumor drug used worldwide against many forms of human cancer. However, in addition to intercalating into the DNA molecule, this drug generates free radicals that induces chromosome aberrations. Fruits of Salanum melongena are rich in flavonoids. Since several flavonoids have been reported to be efficient antioxidants by scavenging oxygen radicals, the objective of the present study was to investigate the possible protective effect of a standardized extract of Solanum melongena on Wistar rat cells treated with DXR in vivo. The animals were treated by gavage with the extract at 50% of the LD 50 (3 g/kg determined for mice) for 10 consecutive days (group 1) and during 1 day (a single dose, group 2), and submitted to euthanasia 24 h after DXR injection (10 mg/kg body weight) for micronucleus assay (MN) and chromosome preparations. Control groups received a single dose of DXR or S. melongena extract. In both treatments where the animals were treated with the extract and with the DXR simultaneously, rat bone marrow cells developed significantly fewer MN and chromosomal aberrations than those treated with DXR alone.

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Influence of novobiocin on <FONT FACE=Symbol>g</font>-irradiation G0-lymphocytes as analyzed by cytogenetic endpoints

Cited by 3 publications

References 30 publications

Integrated Genotoxicity Testing of three anti-infective drugs using the TGx-DDI transcriptomic biomarker and high-throughput CometChip® assay in TK6 cells

Integrated Genotoxicity Testing of three anti-infective drugs using the TGx-DDI transcriptomic biomarker and high-throughput CometChip® assay in TK6 cells

The Effect of Phytohaemagglutinin and Colcemid on the Reliability of the Chromosome Aberration Analysis after Ionizing Radiation Exposure

Standardized Solanum melongena Extract Presents Protective Effects against Chromosomal Aberrations Induced by Doxorubicin in Wistar Rat Bone Marrow Cells

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