scholarly journals Genotoxicity of Some Metal-Based Antineoplastics, Evaluated by SOS Chromotest and Cytogenetic Analysis

1996 ◽  
Vol 3 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Carmen Socaciu ◽  
Loan Pasca ◽  
Cristian Silvestru ◽  
Ionel Haiduc
Keyword(s):  
Chromosomal Aberrations ◽  
Cytogenetic Analysis ◽  
Positive Response ◽  
Metabolic Activation ◽  
Antineoplastic Drugs ◽  
Mutagenic Potential ◽  
E Coli ◽  
Bacterial Cultures ◽  
Sos Chromotest ◽  
Clastogenic Effect

The paper reports the screening results of two metal-based antineoplastic drugs with mutagenic potential, such as Romcis (trademark of Cisplatinum, produced in Romania) and diphenylantimony(III) diisopropyldithiophosphate (PADTF). Their effects were compared with those induced by Cyclophosphamide. Two mutagenicity tests, the SOS Chromotest and cytogenetic analysis were applied. The tests were carried out with or without metabolic activation (addition of S9-mix), either in E. coli PQ 37 cultures, using four doses (0.3, 3, 30 and 300 pmol compound/assay) for the SOS Chromotest or in leukocyte cultures using 0.3 mM from each compound, for cytogenetics. The dose- response relationships and SOSIP values revealed an indirect mutagenic potential for Cyclophosphamide, amplified by S9 mix in bacterial cultures and an antiproliferative, clastogenic effect on lymphocytes. For Romcis and diphenylantimony(III) diisopropyldithiophosphate, a significant positive response by SOS Chromotest was recorded, which correlated with increased frequencies of chromosomal aberrations.

scholarly journals Synthesis and Antibacterial Activity of Quaternary Ammonium 4-Deoxypyridoxine Derivatives

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Nikita V. Shtyrlin ◽  
Sergey V. Sapozhnikov ◽  
Albina S. Galiullina ◽  
Airat R. Kayumov ◽  
Oksana V. Bondar ◽  
...  
Keyword(s):  
Quaternary Ammonium ◽  
Benzalkonium Chloride ◽  
Ames Test ◽  
Kidney Cells ◽  
Mutagenic Potential ◽  
E Coli ◽  
Sos Chromotest ◽  
Cytotoxicity Studies ◽  
Starting Point ◽  
Excellent Activity

A series of novel quaternary ammonium 4-deoxypyridoxine derivatives was synthesized. Two compounds demonstrated excellent activity against a panel of Gram-positive methicillin-resistantS. aureusstrains with MICs in the range of 0.5–2 μg/mL, exceeding the activity of miramistin. At the same time, both compounds were inactive against the Gram-negativeE. coliandP. aeruginosastrains. Cytotoxicity studies on human skin fibroblasts and embryonic kidney cells demonstrated that the active compounds possessed similar toxicity with benzalkonium chloride but were slightly more toxic than miramistin. SOS-chromotest inS. typhimuriumshowed the lack of DNA-damage activity of both compounds; meanwhile, one compound showed some mutagenic potential in the Ames test. The obtained results make the described chemotype a promising starting point for the development of new antibacterial therapies.

scholarly journals Evaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, α-PVP and α-PHP

2021 ◽  
Vol 22 (12) ◽  
pp. 6320
Author(s):  
Monia Lenzi ◽  
Veronica Cocchi ◽  
Sofia Gasperini ◽  
Raffaella Arfè ◽  
Matteo Marti ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Metabolic Activation ◽  
Fold Increase ◽  
Synthetic Cathinones ◽  
The Other ◽  
Oxygen Species ◽  
Genetic Damage ◽  
Mutagenic Potential ◽  
Tk6 Cells ◽  
Mutagenic Effects

Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present work was to evaluate their mutagenicity on TK6 cells. On the basis of cytotoxicity and cytostasis results, we selected the concentrations (35–100 µM) to be used in the further analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by flow cytometry. Mexedrone demonstrated its mutagenic potential contrary to the other two compounds; we then proceeded by repeating the analyzes in the presence of extrinsic metabolic activation in order to check if it was possible to totally exclude the mutagenic capacity for α-PVP and α-PHP. The results demonstrated instead the mutagenicity of their metabolites. We then evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the highlighted effects but the results did not show a statistically significant increase in ROS levels for any of the tested substances. Anyway, our outcomes emphasize the importance of mutagenicity evaluation for a complete assessment of the risk associated with synthetic cathinones exposure.

scholarly journals Assessment of the Mutagenic Activity of Extracts of Brazilian Propolis in Topical Pharmaceutical Formulations on Mammalian CellsIn VitroandIn Vivo

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Juliana Marques Senedese ◽  
Aline Rafaela Rodrigues ◽  
Michelle Andrade Furtado ◽  
Viviane Dias Faustino ◽  
Andresa A. Berretta ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Mutagenic Activity ◽  
Biological Activities ◽  
Antioxidant Properties ◽  
Test System ◽  
Negative Control ◽  
Continuous Treatment ◽  
Mutagenic Potential ◽  
Topical Formulations

Propolis possesses various biological activities such as antibacterial, antifungal, anti-inflammatory, anesthetic and antioxidant properties. A topically applied product based on Brazilian green propolis was developed for the treatment of burns. For such substance to be used more safely in future clinical applications, the present study evaluated the mutagenic potential of topical formulations supplemented with green propolis extract (1.2, 2.4 and 3.6%) based on the analysis of chromosomal aberrations and of micronuclei. In thein vitrostudies, 3-h pulse (G1phase of the cell cycle) and continuous (20 h) treatments were performed. In thein vivoassessment, the animals were injured on the back and then submitted to acute (24 h), subacute (7 days) and subchronic (30 days) treatments consisting of daily dermal applications of gels containing different concentrations of propolis. Similar frequencies of chromosomal aberrations were observed for cultures submitted to 3-h pulse and continuous treatment with gels containing different propolis concentrations and cultures not submitted to any treatment. However, in the continuous treatment cultures treated with the 3.6% propolis gel presented significantly lower mitotic indices than the negative control. No statistically significant differences in the frequencies of micronuclei were observed between animals treated with gels containing different concentrations of propolis and the negative control for the three treatment times. Under the present conditions, topical formulations containing different concentrations of green propolis used for the treatment of burns showed no mutagenic effect in either test system, but 3.6% propolis gel was found to be cytotoxic in thein vitrotest.

scholarly journals A high-resolution allelotype of B-cell chronic lymphocytic leukemia (B-CLL)

Blood ◽  
2002 ◽  
Vol 100 (5) ◽  
pp. 1787-1794 ◽  
Author(s):  
Urban Novak ◽  
Elisabeth Oppliger Leibundgut ◽  
Jörg Hager ◽  
Dominique Mühlematter ◽  
Martine Jotterand ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Chromosomal Aberrations ◽  
Cytogenetic Analysis ◽  
Prognostic Significance ◽  
Genetic Alterations ◽  
Lymphocytic Leukemia ◽  
Accurate Information ◽  
Trisomy 12 ◽  
Cell Chronic Lymphocytic Leukemia

The most frequent chromosomal aberrations in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance. Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) are used for their detection, but cytogenetic analysis is hampered by the low mitotic index of B-CLL cells, and FISH depends on accurate information about candidate regions. We used a set of 400 highly informative microsatellite markers covering all chromosomal arms (allelotyping) and automated polymerase chain reaction (PCR) protocols to screen 46 patients with typical B-CLL for chromosomal aberrations. For validation, we compared data with our conventional karyotype results and fine mapping with conventional single-site PCR. All clonal cytogenetic abnormalities potentially detectable by our microsatellite PCR (eg, del13q14 and trisomy 12) were picked up. Allelotyping revealed additional complex aberrations in patients with both normal and abnormal B-CLL karyotypes. Aberrations detectable in the samples with our microsatellite panel were found on almost all chromosomal arms. We detected new aberrant loci in typical B-CLL, such as allelic losses on 1q, 9q, and 22q in up to 25% of our patients, and allelic imbalances mirroring chromosomal duplications, amplifications, or aneuploidies on 2q, 10p, and 22q in up to 27% of our patients. We conclude that allelotyping with our battery of informative microsatellites is suitable for molecular screening of B-CLL. The technique is well suited for analyses in clinical trials, it provides a comprehensive view of genetic alterations, and it may identify new loci with candidate genes relevant in the molecular biology of B-CLL.

scholarly journals An Evaluation of Anti-Clastogenic Activities for Garlic (Allium Sativum), Turmeric (Curcuma Longa) and Tulsi (Ocimum Tenuiflorum) with Clastogen (Mitomycin) in Human Lymphocytes – A Case Study

2020 ◽  
Vol 5 (1) ◽  
Keyword(s):  
Chromosomal Aberrations ◽  
Whole Blood ◽  
Allium Sativum ◽  
Curcuma Longa ◽  
Human Lymphocytes ◽  
Herbal Extracts ◽  
Ocimum Tenuiflorum ◽  
Clastogenic Effect ◽  
The Individual

Chromosomal aberrations based human syndrome are very critical and sometimes leads to lethality. Such syndrome or disorders are often irreversible. In this present study, we evaluated the preventing effect of herbal extracts from Ocimum (tulsi), Curcuma (turmeric) and Allium (garlic) in developing chromosomal aberrations in whole blood human lymphocytes. The results showed that the clastogenic effect was minimised by the combination of all three herbal extracts compared to the individual extract effects. The spontaneous chromosomal aberrations caused in lymphoma cells were also minimized by the herbal extracts.

scholarly journals Bivariate flow karyotyping in human Philadelphia-positive chronic myelocytic leukemia

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 282-286 ◽  
Author(s):  
GJ Arkesteijn ◽  
AC Martens ◽  
A Hagenbeek
Keyword(s):  
Chromosomal Aberrations ◽  
Cytogenetic Analysis ◽  
Gradient Centrifugation ◽  
Philadelphia Chromosome ◽  
Chromosome Analysis ◽  
Chronic Myelocytic Leukemia ◽  
Translocation Event ◽  
Myelocytic Leukemia ◽  
Conventional Cytogenetic Analysis ◽  
The One

Abstract Chromosome analysis on clinical leukemia material was done by means of flow cytometry (flow karyotyping) to investigate the applicability of this technique in the detection of leukemia-associated abnormalities. Flow karyotyping was performed on blood or bone marrow samples from eight patients with chronic myelocytic leukemia (CML) after a culture period of four days and arresting the cells in metaphase during the last 16 hours. Discontinuous density gradient centrifugation proved to be essential in removing debris and dead cells from the cell suspensions. By this procedure the mitotic index increase ranged from 2 to 80 times initial values. Chromosomes were isolated and stained with two base pair-specific fluorochromes, ie, chromomycin A3 and Hoechst 33258, and run through a specially designed dual-laser beam flow cytometer. Generally, 20,000 chromosomes or more were measured. The data were computer stored in list mode. Besides the clear detection of the specific Philadelphia chromosome, trisomies and other additional chromosomal aberrations [like an i(17q)] were visualized. Quantitative analysis revealed the percentage of subclones containing a certain chromosomal anomaly. Conventional cytogenetic analysis confirmed these findings. In seven of eight cases, CML could be diagnosed on the basis of the presence of a Philadelphia chromosome in the flow karyogram. In one of these seven, the conventional cytogenetic analysis was unknown at that time. The remaining six all matched the standard cytogenetics. The one failure out of eight could be attributed to the specific stimulating conditions in the culture. Although it is impossible by this technique to determine the position of the breakpoint, the involved chromosomes in the translocation event could be identified. In some cases, low percentages of aberrations could not be detected. This study shows that CML can be diagnosed on the basis of flow karyotypic results. Additional chromosomal aberrations can be detected provided that changes in the amount of DNA per chromosome have occurred. Exact quantification of the composition of subclones in the case of mosaicism appear difficult.

Nanomolar Levels of Dimethylsulfoniopropionate, Dimethylsulfonioacetate, and Glycine Betaine Are Sufficient To Confer Osmoprotection to Escherichia coli

1999 ◽  
Vol 65 (8) ◽  
pp. 3304-3311 ◽  
Author(s):  
Anne Cosquer ◽  
Vianney Pichereau ◽  
Jean-Alain Pocard ◽  
Jacques Minet ◽  
Michel Cormier ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Salinity Tolerance ◽  
Glycine Betaine ◽  
Standard Laboratory ◽  
E Coli ◽  
High Affinity ◽  
Bacterial Cultures ◽  
Transport Studies ◽  
Ecological Implications ◽  
Substrate Concentrations

ABSTRACT We combined the use of low inoculation titers (300 ± 100 CFU/ml) and enumeration of culturable cells to measure the osmoprotective potentialities of dimethylsulfoniopropionate (DMSP), dimethylsulfonioacetate (DMSA), and glycine betaine (GB) for salt-stressed cultures of Escherichia coli. Dilute bacterial cultures were grown with osmoprotectant concentrations that encompassed the nanomolar levels of GB and DMSP found in nature and the millimolar levels of osmoprotectants used in standard laboratory osmoprotection bioassays. Nanomolar concentrations of DMSA, DMSP, and GB were sufficient to enhance the salinity tolerance of E. coli cells expressing only the ProU high-affinity general osmoporter. In contrast, nanomolar levels of osmoprotectants were ineffective with a mutant strain (GM50) that expressed only the low-affinity ProP osmoporter. Transport studies showed that DMSA and DMSP, like GB, were taken up via both ProU and ProP. Moreover, ProU displayed higher affinities for the three osmoprotectants than ProP displayed, and ProP, like ProU, displayed much higher affinities for GB and DMSA than for DMSP. Interestingly, ProP did not operate at substrate concentrations of 200 nM or less, whereas ProU operated at concentrations ranging from 1 nM to millimolar levels. Consequently,proU + strains of E. coli, but not the proP + strain GM50, could also scavenge nanomolar levels of GB, DMSA, and DMSP from oligotrophic seawater. The physiological and ecological implications of these observations are discussed.

scholarly journals Subinhibitory Concentrations of Bacteriostatic Antibiotics Induce relA-Dependent and relA-Independent Tolerance to β-Lactams

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Pavel Kudrin ◽  
Vallo Varik ◽  
Sofia Raquel Alves Oliveira ◽  
Jelena Beljantseva ◽  
Teresa Del Peso Santos ◽  
...  
Keyword(s):  
Trna Synthetase ◽  
Growth Stress ◽  
Amino Acid Starvation ◽  
Bacterial Metabolism ◽  
Persister Cells ◽  
Biochemical System ◽  
Content Type ◽  
E Coli ◽  
Bacterial Cultures ◽  
A Site

ABSTRACTThe nucleotide (p)ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance, and virulence. During amino acid starvation, theEscherichia coli(p)ppGpp synthetase RelA is activated by deacylated tRNA in the ribosomal A-site. An increase in (p)ppGpp is believed to drive the formation of antibiotic-tolerant persister cells, prompting the development of strategies to inhibit (p)ppGpp synthesis. We show that in a biochemical system from purifiedE. colicomponents, the antibiotic thiostrepton efficiently inhibits RelA activation by the A-site tRNA. In bacterial cultures, the ribosomal inhibitors thiostrepton, chloramphenicol, and tetracycline all efficiently abolish accumulation of (p)ppGpp induced by the Ile-tRNA synthetase inhibitor mupirocin. This abolishment, however, does not reduce the persister level. In contrast, the combination of dihydrofolate reductase inhibitor trimethoprim with mupirocin, tetracycline, or chloramphenicol leads to ampicillin tolerance. The effect is independent of RelA functionality, specific to β-lactams, and not observed with the fluoroquinolone norfloxacin. These results refine our understanding of (p)ppGpp's role in antibiotic tolerance and persistence and demonstrate unexpected drug interactions that lead to tolerance to bactericidal antibiotics.

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