scholarly journals Genotoxicity of triiodothyronine: Effects on Salmonella typhimurium TA100 and human lymphocytes in vitro

Genetika ◽  
2017 ◽  
Vol 49 (2) ◽  
pp. 387-397
Author(s):  
Jasna Bosnjak-Neumüller ◽  
Ninoslav Djelic ◽  
Milena Radakovic ◽  
Stoimir Kolarevic ◽  
Dragana Mitic-Culafic ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Mammalian Cells ◽  
Ames Test ◽  
Human Lymphocytes ◽  
Genetic Material ◽  
Genotoxic Effects ◽  
Reverse Mutation ◽  
Mutagenic Effects ◽  
Mutation Assay

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.

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
Keyword(s):  
Salmonella Typhimurium ◽  
Cancer Cells ◽  
Ames Test ◽  
Mutagenic Activity ◽  
Resistant Cell ◽  
Biological Targets ◽  
Selective Substitution ◽  
Apoptotic Pathways ◽  
Mutation Assay

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.

Synthesis and mutagenicity of 2-aryl-substitute (o-hydroxy-, m-bromo-, o-methoxy-, o-nitro-phenyl or 4-pyridyl) benzothiazole derivatives on Salmonella typhimurium and human lymphocytes exposed in vitro

Biologia ◽  
2007 ◽  
Vol 62 (5) ◽  
Author(s):  
Berrin Ayaz Tuylu ◽  
Hulya Zeytinoglu ◽  
Ilhan Isikdag
Keyword(s):  
Salmonella Typhimurium ◽  
Sister Chromatid ◽  
Ames Test ◽  
Mutagenic Activity ◽  
Human Lymphocytes ◽  
In Vitro Assays ◽  
Benzothiazole Derivatives ◽  
Replication Index ◽  
Derivatives Of

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.

Evaluation of the mutagenic and genotoxic effects of the ALC67 thiazolidine compound in Salmonella strains and human lymphocytes in vitro

2016 ◽  
Vol 35 (10) ◽  
pp. 1108-1115
Author(s):  
M Charehsaz ◽  
FE Onen-Bayram ◽  
H Sipahi ◽  
K Buran ◽  
AK Giri ◽  
...  
Keyword(s):  
Ames Test ◽  
Human Lymphocytes ◽  
Ethyl Esters ◽  
The Other ◽  
Bacterial Strains ◽  
Anticancer Activities ◽  
Genotoxic Effects ◽  
Antiproliferative Agents ◽  
Chromosomal Aberration Assay

ALC67 is an N-acylated thiazolidine compound with promising anticancer activity that led to the recent discovery of a series of 3-propionyl thiazolidine-4-carboxylic acid ethyl esters as a family of novel antiproliferative agents. Since the mutagenic and genotoxic properties of marketed anticancer molecules constitute a main issue to be addressed, this study focused on the analysis of the mutagenicity, antimutagenecity, and genotoxicity of this molecule. The mutagenicity and antimutagenicity of ALC67 were evaluated by Ames test performed on Salmonella TA98 and TA100 strains. The genotoxicity of this molecule was investigated in the chromosomal aberration assay on human lymphocytes. All results revealed that the analyzed structure is not mutagenic in the two Salmonella strains tested and was not genotoxic in human lymphocytes in vitro. On the other hand, it showed a weak antimutagenic effect in these two bacterial strains. The above results indicate that after performing some more mutagenicity assays using the other recommended strains, this compound can be safely used for the development of new structures exhibiting anticancer activities.

scholarly journals Extracellular and intracellular anti-mutagenic effects of bile pigments in the Salmonella typhimurium reverse mutation assay

2013 ◽  
Vol 27 (1) ◽  
pp. 433-437 ◽  
Author(s):  
C. Mölzer ◽  
H. Huber ◽  
K. Diem ◽  
M. Wallner ◽  
A.C. Bulmer ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Bile Pigments ◽  
Reverse Mutation ◽  
Mutagenic Effects ◽  
Mutation Assay

scholarly journals Transcription of 4′-thioDNA templates to natural RNA in vitro and in mammalian cells

2015 ◽  
Vol 51 (37) ◽  
pp. 7887-7890 ◽  
Author(s):  
Hideto Maruyama ◽  
Kazuhiro Furukawa ◽  
Hiroyuki Kamiya ◽  
Noriaki Minakawa ◽  
Akira Matsuda
Keyword(s):  
Nucleic Acids ◽  
Mammalian Cells ◽  
Genetic Material ◽  
Rna Polymerases ◽  
Chemically Modified ◽  
Biological Studies ◽  
Modified Nucleic Acids

Synthetic chemically modified nucleic acids, which are compatible with DNA/RNA polymerases, have great potential as a genetic material for synthetic biological studies.

Genotoxicity Studies on Sel-Plex®, a Standardized, Registered High-Selenium Yeast

2006 ◽  
Vol 25 (6) ◽  
pp. 477-485 ◽  
Author(s):  
James C. Griffiths ◽  
Ray A. Matulka ◽  
Ronan Power
Keyword(s):  
Chromosome Aberration ◽  
Micronucleus Test ◽  
Mutagenic Activity ◽  
Human Lymphocytes ◽  
Selenium Yeast ◽  
Yeast Saccharomyces Cerevisiae ◽  
Reverse Mutation ◽  
High Selenium ◽  
Chromosome Aberration Test

Selenium, recognized as an essential nutrient for human health, is a component of proteins and enzymes required for various biological functions and is currently being used as a feed supplement for livestock in geographical areas that are naturally low in selenium. Selenium is structurally similar to sulfur, replacing the sulfur atom in stoichiometric amounts and thus functions through an association with proteins, termed selenoproteins. In geographic areas low in selenium, there is the potential for animals (including humans) to become selenium deficient and this potential deficiency can be remedied by consumption of exogenous selenium, including selenium-enriched yeast ( Saccharomyces cerevisiae) that contains high levels of organic selenium (e.g., selenized yeast). A unique, standardized, registered high selenium food-grade baker’s yeast ( S. cerevisiae; Sel-Plex®), was tested in the following battery of Genotoxicity assays; (1) a bacterial reverse mutation test (Ames test); (2) an in vitro mammalian chromosome aberration test; and (3) a mouse micronucleus test. Under the conditions of this assay, Sel-Plex® showed no evidence of mutagenic activity in Salmonella typhimurium, in the bacterial reverse mutation test. Sel-Plex® did not induce significant chromosomal aberrations in cultured human lymphocytes in the in vitro mammalian chromosome aberration test. Sel-Plex® did not statistically increase the frequency or proportion of micronucleated immature erythrocytes in the mouse micronucleus test. Thus, from the studies presented here, the authors conclude that Sel-Plex® is nongenotoxic.

In Vitro Cytotoxicity and Mutagenicity Evaluation of Dental Leucite Glass-Ceramics from Local High Grade Silica Sand

2015 ◽  
Vol 754-755 ◽  
pp. 979-984
Author(s):  
Siti Mazatul Azwa Bt Saiyed Mohd Nurddin ◽  
Malek B. Selamat
Keyword(s):  
Mtt Assay ◽  
Glass Ceramics ◽  
Mutagenic Effect ◽  
Negative Control ◽  
Silica Sand ◽  
High Grade ◽  
Reverse Mutation ◽  
Diphenyl Tetrazolium Bromide ◽  
Mutation Assay

The objective of the study was to determine the degree of biocompatibility of leucite glass-ceramics that have been produced from local high grade silica sand in terms of cytotoxicity and mutagenicity assays. In the present study, the cyctotoxicity and mutagenicity were studied using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay (MTT) and Ames Reverse Mutation. In the MTT assay, a dose response cytotoxicity of leucite sample was evaluated in L929 cells. The cells were treated with the concentrations of 6.25, 12.5, 25.0, 50.00, 100.00 and 200.00 mg/ml of the leucite sample for 24 hours. The cytotoxicity was determined by assessing the cell viability through the reduction of tetrazolium salts (MTT). The mutagenenicity of leucite sample was evaluated inS. typhiriumTA98. TA100, TA1535, TA1537 andE. coliWP2 in the Ames Reverse Mutation assay. Mutagenic effects were evaluated by comparing the mean number of revertant colonies of each extract concentraction with mean number of revertant colonies of the negative control. In results of MTT assay evaluated that the leucite did not show a cytotoxic effect at all concentrations under the condition of the study. Ames Reverse Mutation assay result proven that the leucite sample did not demonstrate a mutagenic effect under the condition of this study withSalmonella typhimuriumandEscherichia coli.

scholarly journals Evaluation of mutagenicity, genotoxicity and chronic toxicity of antiviral drug imidazolyl ethanamide pentandioic acid in in vitro and in vivo test systems

2021 ◽  
Vol 98 (5) ◽  
pp. 548-557
Author(s):  
E. A. Jain ◽  
D. Pleimes ◽  
A. A. Globenko
Keyword(s):  
Oral Administration ◽  
Chromosomal Aberrations ◽  
Ames Test ◽  
Chronic Toxicity ◽  
Micronucleus Test ◽  
Human Lymphocytes ◽  
Antiviral Drug ◽  
Systemic Exposure

Introduction. The antiviral properties of imidazolyl ethanamide pentandioic acid (IPA), the active compound of the drug product, has been proven in various experimental models. However, the literature data on the toxicological properties of IPA are limited.Purpose. To evaluate mutagenic and genotoxic properties in in vitro and in vivo models, as well as to study the toxicity of IPA following chronic oral administration to rats and dogs.Materials and methods. Mutagenic and genotoxic properties of IPA were assessed using the Ames test, the test of chromosomal aberrations in human lymphocytes, and the micronucleus test in rats. The chronic toxicity of IPA was studied in Sprague Dawley rats and beagle dogs of both sexes, to which IPA was administered orally at doses of 30-300 mg/kg/day for 26 and 39 weeks, respectively.Results and discussion. In the Ames test, the addition of IPA up to the maximum dose (5000 mcg/plate) did not result in the increase in the number of revertant colonies. At a concentration of up to 5000 mcg/ml, IPA did not cause chromosomal aberrations in human leukocytes. At doses doses ≤ 2000 mg/kg, IPA did not increase the amount of micronuclei in the bone marrow of rats. In chronic experiments, animals tolerated the administration of IPA well: the dose without an observed effect (NOEL) for rats and dogs was 300 mg/kg/day.Conclusion. IPA did not show mutagenic and genotoxic properties in standard in vitro and in vivo tests. With chronic oral administration to rats and dogs, NOEL IPA equal to 300 mg/kg/day provided a systemic exposure that was 8-10 and 41-65 times higher than that in humans, respectively. The results obtained allow us to consider the safety profile of the prolonged use in humans as favorable.

scholarly journals Genotoxic potential of nonsteroidal hormones

2015 ◽  
Vol 69 (3-4) ◽  
pp. 245-258
Author(s):  
Dijana Topalovic ◽  
Lada Zivkovic ◽  
Ninoslav Djelic ◽  
Vladan Bajic ◽  
Andrea Cabarkapa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Genetic Material ◽  
Experimental Studies ◽  
Genotoxic Effect ◽  
Common Mechanism ◽  
Genotoxic Effects ◽  
Specific Expression ◽  
Study Results

Hormones are cellular products involved in the regulation of a large number of processes in living systems, and which by their actions affect the growth, function and metabolism of cells. Considering that hormones are compounds normally present in the organism, it is important to determine if they can, under certain circumstances, lead to genetic changes in the hereditary material. Numerous experimental studies in vitro and in vivo in different systems, from bacteria to mammals, dealt with the mutagenic and genotoxic effects of hormones. This work presents an overview of the research on genotoxic effects of non?steroidal hormones, although possible changes of genetic material under their influence have not still been known enough, and moreover, investigations on their genotoxic influence have given conflicting results. The study results show that mechanisms of genotoxic effect of nonsteroidal hormones are manifested through the increase of oxidative stress by arising reactive oxygen species. A common mechanism of ROS occurence in thyroid hormones and catecholamines is through metabolic oxidation of their phenolic groups. Manifestation of insulin genotoxic effect is based on production of ROS by activation of NADPH isophorms, while testing oxytocin showed absence of genotoxic effect. Considering that the investigations on genotoxicity of nonsteroidal hormones demonstrated both positive and negative results, the explanation of this discordance involve limitations of test systems themselves, different cell types or biological species used in the experiments, different level of reactivity in vitro and in vivo, as well as possible variations in a tissue-specific expression. Integrated, the provided data contribute to better understanding of genotoxic effect of nonsteroidal hormones and point out to the role and mode of action of these hormones in the process of occurring of effects caused by oxidative stress.

Correction of Genetic Defects in Mammalian Cells by the Input of Small Amounts of Foreign Genetic Material

1973 ◽  
Vol 13 (3) ◽  
pp. 841-861
Author(s):  
YVONNE L. BOYD ◽  
H. HARRIS
Keyword(s):  
Thymidine Kinase ◽  
Mammalian Cells ◽  
Hybrid Cell ◽  
Genetic Material ◽  
Chinese Hamster ◽  
Heat Sensitivity ◽  
Chinese Hamster Cells ◽  
Inosinic Acid ◽  
Mouse Cells

Chinese hamster cells lacking inosinic acid pyrophosphorylase and mouse cells lacking thymidine kinase were fused with chick erythrocytes. The resultant heterokaryons were cultivated in a selective medium in which possession of these enzymes was essential for cell survival and growth. Clones of cells able to grow in this medium were isolated and studied. A detailed karyological analysis of these clones failed to reveal any chick chromosomes; nor could any chick-specific antigens be detected on the surface of the cells. Nonetheless, clones arising from the fusion of chick erythrocytes with Chinese hamster cells were shown to possess an inosinic acid pyrophosphorylase which had the electrophoretic characteristics of chick inosinic acid pyrophosphorylase. However, the clones arising from the fusion of the chick erythrocytes with the mouse cells had a thymidine kinase with the electrophoretic mobility and heat sensitivity of murine, not chick, thymidine kinase. Both types of hybrid cell have now been cultivated in vitro for 18 months without the loss of thymidine kinase or inosinic acid pyrophosphorylase activity.

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