scholarly journals Mutagenic Tests Confirm That New Acetylacetonate Pt(II) Complexes Induce Apoptosis in Cancer Cells Interacting with Nongenomic Biological Targets

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Sandra Angelica De Pascali ◽  
Federica Lugoli ◽  
Antonella De Donno ◽  
Francesco Paolo Fanizzi

New platinum(II) complexes [PtCl(O,O′-acac)(L)] (1) and [Pt(O,O′-acac)(-acac)(L)] (2) (, a; DMS, b) containing a single chelated (O,O′-acac) (1), or one chelated and one -bonded (-acac) acetylacetonate (2) have been synthesized. The new Pt(II) complexes exhibited high in vitro cytotoxicity on cisplatin sensitive and resistant cell lines and showed negligible reactivity with nucleobases (Guo and 5′-GMP) but selective substitution of DMSO/DMS with soft biological nucleophiles, such as L-methionine. In order to assess the ability of the new complexes with respect to cisplatin to induce apoptosis by interaction with nongenomic targets, the Ames' test, a standard reverse mutation assay, was carried out on two Salmonella typhimurium strains (TA98 and TA100). Interestingly, the new complexes did not show the well-known mutagenic activity exhibited by cisplatin and are, therefore, able to activate apoptotic pathways without interacting with DNA.

2010 ◽  
Vol 1 (1) ◽  
pp. 55 ◽  
Author(s):  
Akram Hassan ◽  
S.A Omar ◽  
Zaihan Ariffin

Silver amalgam/Silverfil Argentum® is a ‘Malaysian made amalgam’ has already been approved to be free from cytotoxicity, however its genotoxic effect has not been explored yet as biocompatible material. The objective of this study was to identify the genotoxic characteristic of silver amalgam by using Bacterial Reverse Mutation Assay (Ames test). This was a descriptive experimental study involving one strain of mutated Salmonella. The test material was evaluated in one mutated strain of Salmonella typhimurium TA1538 with and without an external metabolic activation system (S9 Mix). The bacteria were incubated for 48 hours at 37±0.5ºC before the colony growth or revertant colonies were counted. Data obtained were analyzed by using non-statistical method. The investigation of the genotoxic reaction on the test material revealed thatthe number of revertant colonies in both strains with and without S9 Mix were less than twice of the negative control even in the presence of high silver amalgam concentrations (5.0μg/ml). This study demonstratedthat the test material did not exhibit any mutagenic activity under the chosen conditions. Thus, silver amalgam could be considered to have no genotoxicity effect.


2008 ◽  
Vol 6 (4) ◽  
pp. 29-33 ◽  
Author(s):  
Nazira S Karamova ◽  
Alexandra P Denisova ◽  
Zenon Stasevski

The mutagenic activity of five pesticides actara, sencor, mospilan, pencozeb, fastac widely used for treatment of potato plant lands in Tatarstan was tested in the Ames test. The non toxic concentrations of the pesticides determined in preliminary cytotoxicty test were used in the Ames assay. Pesticides actara, mospilan, pencozeb, fastac did not show mutagenic effect in Salmonella typhimurium TA 100 without rat liver S9 fraction. The weak mutagenic effect of herbicide sencor was established at concentration 1 ug/plate. Metabolic activation in vitro using rat liver S9 fraction decreased the mutagenic activity of sencor and did not alter the mutagenicity rate of the pesticides actara, mospilan, pencozeb and fastac.


Biologia ◽  
2007 ◽  
Vol 62 (5) ◽  
Author(s):  
Berrin Ayaz Tuylu ◽  
Hulya Zeytinoglu ◽  
Ilhan Isikdag

AbstractDerivatives of 2-aryl-substitute (o-hydroxy-, m-bromo-, o-methoxy-, o-nitro-phenyl or 4-pyridyl) benzothiazole were synthesized and tested for their mutagenicity in in vitro assays: (i) in the Ames test with Salmonella typhimurium TA98 and TA100 strains; and (ii) in the sister chromatid exchange (SCE) in cultured human lymphocytes. The four of compounds (BT-11, B-12, BT-14 and BT-15) caused statistically significant increase in revertant colonies of TA98 and TA100. Treatment of lymphocytes with compounds also caused a significant increase in SCE/cell in association with high levels and long exposure (300 µg/mL and 48 h) of the four compounds. It can be concluded that benzothiazole derivatives showed mutagenic activity and were also able to exert a genotoxic effect reducing both the replication index and mitotic index.


Genetika ◽  
2017 ◽  
Vol 49 (2) ◽  
pp. 387-397
Author(s):  
Jasna Bosnjak-Neumüller ◽  
Ninoslav Djelic ◽  
Milena Radakovic ◽  
Stoimir Kolarevic ◽  
Dragana Mitic-Culafic ◽  
...  

There is increasing evidence that substances which are normally present in human or animal bodies may, under the certain circumstances, exhibit deleterious effects on genetic material, therefore acting as endogenous mutagenic agents. Since hormones represent one of the best studied endogenous mutagens, some research focused on the possible role of thyroid hormone in mutagenesis and carcinogenesis. Indeed, thyroid hormones accelerate aerobic metabolism and production of reactive oxygen species (ROS) and, therefore, may exhibit mutagenic effects in various test systems on mammalian cells. However, possible mutagenic effects on prokaryotic DNA has not been investigated so far. Hence, the aim of this research was to compare the sensitivity of TA 100 Salmonella typhimurium with and without metabolic activation with S9 fraction, and human lymphocytes to possible genotoxic effects of triiodothyronine (T3). Therefore, we used the reverse mutation assay on S. typhimurium (Ames test) and in vitro Comet assay in isolated peripheral blood human lymphocytes. In both tests-systems a broad spectrum of T3 concentrations was applied. The obtained results showed absence of genotoxic effects of T3 in bacterial reverse mutation assay and very profound genotoxic effects in human lymphocytes at concentrations higher than 15 ?M. We only observed cytotoxic effects in bacterial system at very high T3 concentrations (300 and 500 ?M). In conclusion, T3 was unable to increase the level of reverse mutations in Ames test both with and without S9 mix. Therefore, it seems that ROS production in mitochondria may be the primary cause of DNA damage caused by T3 in mammalian cells.


Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1553
Author(s):  
Ming-Wei Chao ◽  
Chia-Yi Tseng ◽  
Pei-Ying Lin ◽  
Yu-Jung Chang ◽  
Özge Köse ◽  
...  

Exposure to 3,5-dimethylaminophenol (3,5-DMAP), the metabolite of the 3-5-dimethylaniline, was shown to cause high levels of oxidative stress in different cells. However, we have shown that this alkylaniline metabolite was non-mutagenic to different strains of Salmonella typhimurium in Ames test and also was found to be not mutagenic to CHO cells in HPRT test. Concerning all the available data, we aimed to observe whether this metabolite may have anti-carcinogenic potential in human non-small cell lung cancer line (A549 cells). 3,5-DMAP caused a dose-dependent increase in cytotoxicity and generation of superoxide (O2-.) and reactive oxygen species (ROS). 3,5-DMAP did not produce significant cytotoxicity to human lung fibroblasts even at very high concentrations; however showed higher cytotoxic effect on A549 lung cancer cells at the same concentrations. 3,5-DMAP also led to molecular events, like increases in apoptotic markers (i.e., p53, Bad, Bax and cytochrome and decreases anti-apoptotic proteins (Bcl-2). Furthermore, 3,5-DMAP provided significant decreases in cell viability of A549 cells and eventually inhibited growth of A549 cells in an in vivo mouse model. Tumor sections showed that 3,5-DMAP down-regulated c-Myc expression but up-regulated p53 and cytochrome c, all of which might result in tumor growth arrest. In conclusion, our findings demonstrate 3,5-DMAP is not mutagenic to Salmonella typhimurium and CHO cells; toxic to A549 cells and therefore may have anti-cancer properties, the importance of which should be elucidated with further mechanistic studies.


2018 ◽  
Vol 245 ◽  
pp. 18002 ◽  
Author(s):  
Olga Ivanchenko ◽  
Rustem Khabibullin ◽  
Rahat Bhat

Environmental pollution and ecosystem dysfunction are one of the most important problems of the today’s world. Assessment of toxigenic properties of effluents from the meat-processing enterprise was carried out using the short-term microorganisms biotests in vitro. Both native waste water and its ether and water fractions were investigated. The probes’ sterilization was carried out by filtration through the sterile membrane filters Synpor with pores diameter of 0.45 m. Mutagenic activity of wastewaters was determined using the Salmonella/microsomes plate with in vitro metabolic activation and without metabolic activation (Ames test). As a metobolic activation the rat liver microsomes were used. Studying of the DNA-damaging activity was carried out using the suspension method modification on the mutant Escherichia coli strains, in which the functioning of one reparation systems is suppressed: uvrA-, recAand рol A-. Native waste water doesn’t have an influence on the mutant strains recAand рol A-, its survivability degree is in the range 96-100%. However, DNA-damaging action was registered for the strain with the damaged excision repair (uvrA-), survivability of which was 81.31%. Ames test of wastewater and its fractions didn’t reveal any mutagenic activity. The tests used in this work allow one to comprehensively estimate the genetic danger of the enterprise wastewaters within a short time and are recommended as test-systems for monitoring the ecological safety of wastewaters.


10.17158/232 ◽  
2012 ◽  
Vol 18 (1) ◽  
Author(s):  
Judee N. Nogodula ◽  
Jessa Marie D. Draug ◽  
Maryjane S. Jamero

Taro (Colocasia esculenta) plant is commonly available and popularly used as food and alternative medicine. To prove its medicinal value, the study explored its secondary metabolites from aqueous-ethanolic leaf extract. Specifically, this investigation aimed to classify its acute dermal toxicity and antibacterial activity, determine its Minimum Inhibitory Concentration (MIC), and identify the equipotency with the standard drug and mutagenic activity. Phytochemical screening of tannins, alkaloids, saponins, cardenolides and bufadienolides, flavonoids, polyphenol compounds and anthraquinones was performed. Five healthy female rabbits were used for toxicity test based on OECD guidelines 404. Kirby-Bauer method was employed for antibacterial activity (susceptibility and potency tests) using Methicillin-Resistant Staphylococcus aureus ATCC 43300, Clinical Isolate Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. A two-fold agar dilution was applied for Minimum Inhibitory Concentration and Ames test was employed for direct mutagenicity assay using Salmonella typhimurium TA98. Results showed that leaf extract has no anthraquinone and it is categorized as non toxic up to allowable dose of 5000 mg/kg. The findings showed a significant difference on the mean zones of inhibition between Vancomycin and plant extract against S. aureus and between tetracycline and the extract towards E.coli. The MRSA and P. aeruginosa showed no significant differences. The MIC of extract is effective to MRSA and S. aureus at 105.26 and 50 mg/mL respectively. However, E. coli and P. aeruginosa are resistant up to the 105.26 mg/mL. Potency test revealed a non-comparability in strength between the extract and Azithromycin using Gram-negative bacteria. However, the extract showed comparable strength with the standard drug using MRSA and S. aureus. Ames test revealed a mutagenic activity using Salmonella typhimurium TA98.


Author(s):  
Rin S. Mukhammadiev ◽  
◽  
Rish S. Mukhammadiev ◽  
L.R. Valiullin ◽  
N.R. Kasanova ◽  
...  

The mutagenic activity of the drug based on strains of lactic acid and propionic acid microorganisms showed that the studied drug and its metabolites did not induce reverse mutations from histidine auxotrophy to prototrophy in histidine-dependent Salmonella typhimurium TA98 and TA100 strains. The number of revertant colonies in the experiment and control differed significantly less than 2.0 times. The drug had a low MI of 1.0-1.1 for the TA98 strain and 0.96-1.07 for the TA100 strain. The data obtained indicate the safety of the drug based on lactic acid and propionic acid microorganisms, as well as the possibility of its further use in agriculture and veterinary medicine.


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