scholarly journals Mutagenic Study of Benzimidazole Derivatives with (+S9) and without (−S9) Metabolic Activation

2019 ◽  
Vol 20 (18) ◽  
pp. 4324
Author(s):  
Nurul Hafizan Azahar ◽  
Siti Soleha Ab dullah ◽  
Rozaini Abdullah ◽  
Norizan Ahmat ◽  
Abdah Md Akim ◽  
...  
Keyword(s):  
Ames Test ◽  
Mutagenic Activity ◽  
Biological Activities ◽  
Metabolic Activation ◽  
Benzimidazole Derivatives ◽  
Ortho Position ◽  
Bacterial Strains ◽  
Diverse Range ◽  
Structure Activity ◽  
Plasmid Pkm101

Benzimidazole derivatives have a diverse range of biological activities, including antiulcer, antihypertensive, antiviral, antifungal, anti-inflammatory, and anticancer. Despite these activities, previous studies have revealed that some of the derivatives can induce mutations. This study aimed to screen for potential mutagenic activities of novel benzimidazole derivatives 1–4 using the Ames test and to study their structure–activity relationship (SAR). An Ames test was carried out on two strains of Salmonella typhimurium (TA98 and TA100) in the absence and presence of metabolic activation. Genetic analysis was performed prior to the Ames test to determine the genotypes of the bacterial tester strains. Both bacterial strains showed dependency on histidine with the presence of rfa mutation, uvrB deletion, and plasmid pKM101. Further, all derivatives tested showed no mutagenic activity in the absence of metabolic activation in both tester strains. However, in the presence of metabolic activation, compound 1 appeared to induce mutation at 2.5 µg/plate when tested against the TA98 strain. These results suggest that the absence of the -OH group at the ortho-position over the phenyl ring might be the cause of increased mutagenic activity in compound 1. Additionally, the presence of mutagenic activity in compound 1 when it was metabolically activated indicates that this compound is a promutagen.

scholarly journals The Mutagenicity and Antimutagenicity of Canarium odontophyllum (Dabai) Acetone Leaves Extracts

2017 ◽  
Vol 9 (13) ◽  
pp. 62
Author(s):  
Ahmad Rohi Ghazali ◽  
Farah Mardhiah Khairuddin ◽  
Tava Shelan Nagapan ◽  
Dayang Fredalina Basri
Keyword(s):  
Ames Test ◽  
Mutagenic Activity ◽  
Biological Activities ◽  
Negative Control ◽  
Antimutagenic Activity ◽  
Bacterial Strains ◽  
Mutagenicity Assay ◽  
Control Plate ◽  
Canarium Odontophyllum ◽  
Acetone Extracts

Canarium odontophyllum or locally known as Dabai in Sarawak is a fruit largely consumed by the locals. Based on previous studies, the plant possessed various biological activities, such as antimicrobial, antioxidant, antifungal and anticancer. Our aim was to investigate the mutagenicity and antimutagenicity of C. odontophyllum acetone leaves extracts by using the Ames test (Salmonella reverse mutagenicity assay).The Ames test also involved the pre-incubation method against Salmonella typhimurium TA98 and TA100 bacterial strains in the absence and presence of metabolic activator S9 system. C. odontophyllum crude acetone extracts were diluted with 10% DMSO to obtain three different concentrations of 3.125, 12.5 and 50 mg/ml. To determine the mutagenicity effects of the extracts, each concentration of the extract was evaluated based on the two-fold value of the number of revertant’s colony in negative control plate as the cut-of point. No mutagenic activity was observed for the frameshift mutation (TA98) and base-pair substitution mutation (TA100) in all concentrations of C. odontophyllum in the presence and absence of metabolic activator S9 system. Antimutagenicity test was carried out to determine the potential of C. odontophyllum extracts to inhibit the mutation induced by specific mutagens. The highest antimutagenic activity was seen in the presence of metabolic activator S9 system with inhibition percentage greater than 50% in both bacteria strains TA98 (62.38%) and TA100 (58.24%). In conclusion, C. odontophyllum acetone leaves extract was not mutagenic and had significant inhibitory effects on mutagenicity in both bacterial strains with and without the metabolic activator S9 system. Our results could contribute to the safe use of C. odontophyllum. In addition, based on the significant antimutagenic activity demonstrated by the C. odontophyllum acetone leaves extracts, the extract could also be developed as a chemopreventive agent.

scholarly journals Antimutagenic activity of raw materials and by-products by production of grape wines

2009 ◽  
Vol 26 (Special Issue) ◽  
pp. S55-S59
Author(s):  
J. Totušek ◽  
D. Lefnerová ◽  
M. Kyseláková ◽  
J. Balík ◽  
J. Veverka ◽  
...  
Keyword(s):  
Botrytis Cinerea ◽  
Ames Test ◽  
Raw Materials ◽  
Experimental System ◽  
Metabolic Activation ◽  
Antimutagenic Activity ◽  
Bacterial Strains ◽  
Methanolic Extracts ◽  
Increased Risk ◽  
By Products

The inhibition of mutagenicity was assessed by Ames test by bacterial strains <i>Salmonella typhimurium</i> TA98 and TA100 using two mutagens and methanolic extracts of healthy fresh berries of blue grapevine varieties – St. Laurent, Portugal, André and white varieties – Chardonnay, Welschriesling, Pinot Gris and berries infected with <i>Botrytis cinerea</i> fungus. As model mutagens, two compounds whose presence in food is real, 2-amino-3-methyl-3H-imidazo-(4.5-f-)-quinoline (IQ), arising from certain heat treatments of meat and acting as indirect mutagen after metabolic activation, and N-nitroso-N-methylurea (MNU) acting as a direct mutagen, were applied. An increased risk of MNU is due to its possible endogenous formation. Fermentation sediment after vinification of the varieties Chardonnay, Welschriesling and André was tested by similar experimental system. All extracts showed strong positive inhibition of mutagenicity, berries infested with Botrytis cinerea also in diluted extracts. Positive inhibition was demonstrated also by fermentation sludge.

scholarly journals Wastewaters of meat-processing enterprise: assessment of genotoxic potential

2018 ◽  
Vol 245 ◽  
pp. 18002 ◽  
Author(s):  
Olga Ivanchenko ◽  
Rustem Khabibullin ◽  
Rahat Bhat
Keyword(s):  
Waste Water ◽  
Ames Test ◽  
Excision Repair ◽  
Mutagenic Activity ◽  
Liver Microsomes ◽  
Metabolic Activation ◽  
Rat Liver Microsomes ◽  
Meat Processing ◽  
Processing Enterprise

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.

scholarly journals An in vitro genotoxicity study of silver amalgam on Ames test

2010 ◽  
Vol 1 (1) ◽  
pp. 55 ◽  
Author(s):  
Akram Hassan ◽  
S.A Omar ◽  
Zaihan Ariffin
Keyword(s):  
Ames Test ◽  
Mutagenic Activity ◽  
Metabolic Activation ◽  
Colony Growth ◽  
Negative Control ◽  
Test Material ◽  
Silver Amalgam ◽  
Mutation Assay ◽  
In Vitro Genotoxicity

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.

scholarly journals Evaluation of mutagenic activity of the pesticides: actara, sencor, mospilan, pencozeb, fastac in the Ames test

2008 ◽  
Vol 6 (4) ◽  
pp. 29-33 ◽  
Author(s):  
Nazira S Karamova ◽  
Alexandra P Denisova ◽  
Zenon Stasevski
Keyword(s):  
Salmonella Typhimurium ◽  
Rat Liver ◽  
Potato Plant ◽  
Ames Test ◽  
Mutagenic Activity ◽  
Metabolic Activation ◽  
Mutagenic Effect ◽  
Toxic Concentrations ◽  
S9 Fraction

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.

Genotoxicity Testing of Cooked Cured Meat Pigment (CCMP) and Meat Emulsion Coagulates Prepared with CCMP

2000 ◽  
Vol 63 (7) ◽  
pp. 945-952 ◽  
Author(s):  
M. STEVANOVIĆ ◽  
P. ČADEŽ ◽  
B. ŽLENDER ◽  
M. FILIPIČ
Keyword(s):  
Salmonella Typhimurium ◽  
Ames Test ◽  
Mutagenic Activity ◽  
Metabolic Activation ◽  
Meat Emulsion ◽  
Color Development ◽  
Umu Test ◽  
Musculus Quadriceps ◽  
Cured Meat ◽  
Residual Nitrite

The preformed cooked cured meat pigment (CCMP) synthesized directly from bovine red blood cells or through a hemin intermediate was found to be a viable colorant for application to comminuted pork as a nitrite substitute. However the genotoxicity of CCMP and meat emulsion coagulates prepared with CCMP has not been evaluated. Therefore the objectives of this work were to investigate genotoxicity of CCMP and the influence of CCMP addition on genotoxicity and the content of residual nitrite in model meat emulsion coagulates. Meat emulsions were prepared from white (musculus longissimus dorsi) and red (musculus quadriceps femoris) pork muscles with two different amounts of synthesized pigment CCMP. Comparatively, emulsions with fixed addition of nitrite salt and emulsions without any addition for color development were made. Genotoxicity of CCMP and meat emulsion coagulates was tested with the SOS/umu test and the Ames test. Neither CCMP nor meat emulsion coagulates prepared with CCMP or nitrite salt were genotoxic in the SOS/umu test. In the Ames test using Salmonella Typhimurium strains TA98 and TA100 samples of coagulates prepared with CCMP and with nitrite showed weak mutagenic activity in Salmonella Typhimurium strain TA100 but only in the absence of the metabolic activation, while CCMP was not mutagenic. Coagulates prepared with CCMP contained significantly less residual nitrite than coagulates prepared with nitrite salt. These results indicate that from the human health standpoint the substitution of nitrite salt with CCMP would be highly recommendable.

scholarly journals Assessment of experimental conditions affecting spontaneous mutation level of Salmonella strains used in the Ames test

2021 ◽  
Vol 100 (7) ◽  
pp. 736-743
Author(s):  
Olga V. Egorova ◽  
Yuliya V. Demidova ◽  
Nataliya A. Ilyushina
Keyword(s):  
Ames Test ◽  
Mutagenic Activity ◽  
Spontaneous Mutation ◽  
Gene Mutations ◽  
Metabolic Activation ◽  
Negative Control ◽  
Selective Medium ◽  
Gelling Agent ◽  
Experimental Conditions ◽  
Factors Affecting

Introduction. The bacterial reverse gene mutations test (the Ames test) is widely used to assess chemicals’ mutagenic activity. The spontaneous mutation level of test strains is a mandatory characteristic that has to be monitored in a laboratory performing mutagenicity studies using the Ames test. In this regard, it is important to assess the factors affecting the spontaneous mutation level in the experiment and, therefore, on the general conclusion on the test item mutagenicity. Material and methods. A plate incorporation test version was used both in the presence and absence of a metabolic activation system. Results. We summarized the historical control data obtained in the laboratory in 2016-2020, determine the fluctuation limits in the number of revertant colonies for each strain, and identify the factors affecting the negative control variability. No significant differences were found in the spontaneous background of test strains when using DMSO or water as solvents, polypropylene or polystyrene tubes, as well as Petri dishes of different types. In the case of the TA1535, TA102 and TA100 cultures, no influence of the presence of the S9 mixture on the spontaneous reversion range was revealed (p≤0.05). Statistically significant differences in the number of spontaneous revertants (at + S9 or -S9) were found for the strains that allow detecting frameshift mutations, TA97 and TA98. It has been shown that the volume of the selective medium and the brand of gelling agent in its composition are important factors leading to the variability of the historical negative control. Conclusion. To ensure the quality of experiments according to the principles of good laboratory practice and the reliability of the data obtained using the bacterial reverse mutation method, it is necessary to standardize the operations in advance of experiments.

Indole derivatives as anti-tubercular agents: An overview on their synthesis and biological activities

2020 ◽  
Vol 27 ◽  
Author(s):  
Gangireddy Sujeevan Reddy ◽  
Manojit Pal
Keyword(s):  
Biological Activities ◽  
Indole Derivatives ◽  
Bacterial Strains ◽  
Diverse Range ◽  
In Silico Studies ◽  
Peptide Derivatives ◽  
Pharmacological Target ◽  
Bioactive Agents

Background: The indole framework is considered as one of the privileged structures in the area of medicinal chemistry and drug discovery because compounds containing this framework have shown to possess remarkable ability to bind with many receptors or proteins with high affinity. It is therefore not surprising that indole nucleus is a frequently found moiety in many bioactive agents or drugs. Indole derivatives have also been explored or studied for their anti-tubercular properties for a long time. The growth inhibition of Mycobacterium tuberculosis (MTB) in vitro and in vivo by the gut microbiota metabolite indole propionic acid (IPA) is one of the recent examples. Notably, tuberculosis (TB) an intractable disease and a major cause of death worldwide have caused an alarming rise in the number of TB cases recently because of two main reasons e.g. a several-fold rise among HIV-infected patients and increased drug resistance by some bacterial strains. Thus identification of new agents or potential drugs against TB is urgently needed. Methods: While the specific pharmacological target or mechanism of action (MOA) for anti-tubercular activities has been reported for many indole derivatives, the MOA is not well defined or known for a number of indole derivatives though they were found to be active against MTB. In the current review article we have focused on both types of indole derivatives that have shown activities against MTB. The indoles with known MOA are further segregated based on this pharmacological target reported or indicated whereas other indoles are classified based on the type of anti-TB properties shown by them. The literature for last 20 years as well as related to up to date knowledge and information was searched on Pubmed, Google Scholar, MEDLINE and various other databases till August 2020. Results: A diverse range of functionalized indole derivatives such as indole based alkaloids, simple indoles, fused indoles, amide / peptide derivatives of indole, isatin derivatives etc have been reported to possess anti-tubercular activities. The anti-tubercular activities, in silico studies (if reported) and the chemical syntheses (in most of the cases) of representative indole derivatives are presented briefly in the current article. The papers referenced by this review allow a deep analysis of status of the indole based anti-tubercular agents explored over the past two decades. Conclusion: This review aims at stimulating renewed interest and effort in the discovery and development of new indole-based agents or potential drugs for the treatment of TB. The emergences of modern methods especially that based on transition metal catalysed reactions have opened up tremendous opportunities in the area of indole synthesis. The desired goal would be to have utilized these modern methodologies for the identification of potent and promising agents to fight against MTB.

Acute and Genotoxic Profile of a Dimeric Impurity of Cefotaxime

2004 ◽  
Vol 23 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Shiv Kumar Agarwal ◽  
Upendra Bhatnagar ◽  
Navin Rajesh
Keyword(s):  
Mammalian Cells ◽  
Mutagenic Activity ◽  
Clinical Signs ◽  
Chinese Hamster ◽  
Metabolic Activation ◽  
Sprague Dawley ◽  
Bacterial Strains ◽  
Sprague Dawley Rats ◽  
A Cell

The manufacturing and storage of cefotaxime produces different impurities of various concentrations, which may influence the efficacy and safety of the drugs. Because no report of toxicity data is available on the impurities of cefotaxime, the present acute and genotoxicity studies were designed and conducted to provide the information for establishing the safety profile and qualification of the dimeric impurity. Histidine-requiring mutants of Salmonella typhimurium TA97a, TA98, TA100, TA102, and TA1535 strains, with or without metabolic activation (S-9), were used for point-mutation tests. Neither increase in numbers of revertants, indicative of mutagenic activity, nor inhibition of bacterial growth, indicative of cytotoxicity, was observed when the dimeric impurity of cefotaxime at concentrations of 0.62, 1.85, 5.56, 16.67, and 50 μg/plate was incorporated into plates containing S. typhimurium bacterial strains. Cultures of Chinese hamster ovary (CHO) cells at a cell density of 2 × 105 cells per culture were exposed to the dimeric impurity of cefotaxime at the concentration of 11.25, 22.5, and 45 mg per culture, with or without metabolic activation, and harvested at 18 h after exposure. No chromosomal aberrations in the cultured mammalian cells were recorded. Acute intramuscular administration of the dimeric impurity of cefotaxime in Sprague-Dawley rats did not result in any clinical signs and gross pathological changes up to 2000 mg/kg-body weight. The results of these studies indicated that the dimeric impurity of cefotaxime is nonmutagenic in Ames test, nonclastogenic in vitro, and acutely nontoxic in rats.

scholarly journals Mutagenic and Cytotoxic Activity of Insecticide Napoleon 4EC in Allium cepa and Ames Test

Caryologia ◽  
2021 ◽  
Author(s):  
Dilek Akyıl
Keyword(s):  
Allium Cepa ◽  
Ames Test ◽  
Mutagenic Activity ◽  
Insect Pest ◽  
Test Group ◽  
Metabolic Activation ◽  
Negative Control ◽  
Root Tip ◽  
Control Group ◽  
Cytotoxic Effects

The objective of this study was to explore the mutagenic and cytotoxic effects of Napoleon 4EC pesticide used in Turkey to control insect pest by using two standard assays. The Allium cepa test was used for determined the cytotoxic effects of this pesticide. For this test, onion seeds were exposed to Napoleon 4EC (100, 200, and 400 ppm) for 24, 48, and 72 hours. For each test group root tip cells were stained with Feulgen and five slides were prepared for each concentration and counted microscopically. The concentrations Napoleon 4EC was compared with the value for the negative control using Dunnet-t test, 2 sided. The results indicated that mitotic index was clearly decreased with increasing the concentration of Napoleon 4EC in each treatment group as compared to the controls. The percentage of mitotic phases has been markedly impacted. Five different doses of the pesticide (50, 100, 200, 400, 800 μg/plate) were examined with Ames test using Salmonella typhimurium strains TA98 and TA100 with and without S9 metabolic activation for mutagenic activity. Ames test results showed a dose dependent effect, but not twice the negative control for S. typhimurium TA98 and TA100, with or without S9 mix except 800 μg/plate doses. In 800 μg/plate doses, colony numbers are two-fold increase according to colony number of control group. So, this places the this compound as a weak mutagen according to the parameters.

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