Nitropyridoindoles—Formation,characterization and mutagenicity

Nitration of pyridoindoles (β‐carbolines) was carried out using different nitration methods and structural assignments of these nitro compounds were made using different spectroscopic techniques. The mutagenic activity of these nitro derivatives was studied using Salmonella typhimurium strains TA 98 NR and TA 100 NR in the absence as well as in the presence of S‐9 mix. Only trinitro derivatives were found to be highly mutagenic to strain TA 98 NR.     

Mutagenicity assessment of textile dyes from Sanganer (Rajasthan)

Sanganer town, district Jaipur (Rajasthan, India) is famous worldwide for its hand block dyeing and textile printing industries. These industries use a variety of chemicals and dyes during processing and finishing of raw materials. Most of the textile dyes used by these industries have not been evaluated for their impact on health and the environment. The workers in these industries are exposed to such dyes with no control over the length and frequency of exposure. Further, untreated and sometimes even treated effluents from these industries are released into surface waters of Amani Shah drainage or through the drainage systems, seep into the ground water and adjoining water bodies. Since many textile dyes are known carcinogens and mutagens, a complete evaluation of the safety of these dyes in the human environment must include an evaluation of their genotoxicity or mutagenicity. A total of 12 textile dyes from Sanganer were tested for their mutagenicity, by Ames Salmonella reversion assay using strain TA 100 of Salmonella typhimurium. Only 1 dye, Red 12 B showed absence of mutagenic activity. The remaining 11 dyes were all positively mutagenic.     

Modification of mutagenic activity of benzo[a]pyrene by trace elements in the Ames assay

Benzo[a]pyrene (BaP) is one of the most ubiquitous environmental contaminants and exerts potent carcinogenicity and mutagenicity. In the presence of rat liver S9 mix, four trace elements, germanium (Ge), iron (Fe), zinc (Zn), and molybdenium (Mo), were included in the Ames Salmonella microsome/mutagenic assay to test their inhibitory effects on BaP-induced mutations. All trace elements were found to exert an inhibitory effect in tester TA98 and TA100 strains; Fe was the most potent among the elements tested, whereas Zn was weakly inhibitory to prevent mutations. The present findings demonstrate that the antimutagenic potential of trace elements, notably Fe, may be attributed to its modulatory effect on the bioactivation and detoxification processes of BaP.     

Synthesis of 2,5‐diaryl‐2,4‐pentadienenitriles and their spectral,fluorescence and mutagenic properties

The condensation of substituted cinnamaldehydes and arylacetonitriles using sodium ethoxide in ethanol at room temperature afforded 2,5‐diaryl‐2,4‐pentadienenitriles in good yield. The structure of the reaction products was established on the basis of their infrared, nuclear magnetic resonance and elemental analysis data. Two representative compounds were studied for their mutagenic activity. One of them showed a weak mutagenicity while the second showed a high mutagenic activity in TA97a Salmonella strain. Both were negative in TA100. Some of these pentadienenitriles showed fluorescence in solutions.     

Analyses of PAHs (polycyclic aromatic hydrocarbons) and mutagenicity in raw and chlorinated water

Both raw water and chlorinated drinking water samples were collected from and the Liu‐Du water treatment plant in northern Taiwan from October 1990 to April 1992. The polycyclic aromatic hydrocarbons (PAHs) and mutagenicity in these water samples were analyzed by GC/MS and Ames test. The Mutagenicity/DMSO (Dimethyl Sulfoxide) ratio in S. typhimurium TA98 and TA100 with or without S9 mixture increased, even higher than 2, following the sequence of unit process. It was observed that the mutagenicity with TA98 (S9+) was highly related to most of PAHs in the raw water; while the mutagenicity with TA98 (S9+) was only correlated with DbA and BghiPr in the treated water. It could be expected that the mutagenicity level was controlled by other predominant components after the raw water was treated, for example, the chlorination process.     

Antimutagenic and bacteriostatic activities of Schiff‐base compounds derived from aminoguanidine,semicarbazone and thiosemicarbazone and a copper(II)‐coordination complex

The Schiff‐base aminoguanidine compounds including a resorcylidene aminoguanidine copper(II) complex that were synthesized at our laboratory posses non‐mutagenic properties when tested with Ames test using Salmonella typhimurium TA97, TA100 and TA102 bacterial strains. These compounds were tested as possible pharmacological agents in preventing a wide array of illnesses. Additionally, some of these compounds exhibit strong antimutagenic and bacteriostatic activity. Nitrovin, a known mutagen, was used in the antimutagenicity tests as the inducer. A three‐dimensional projection of the copper(II) complex was derived by the semi‐empirical method ZINDO/1 to obtain additional information about its structure, and to help elucidate a possible mechanism of action.     

Evaluation of the antimutagenic and antiradical potentials of extracts from the tubers of (Tunisian) Cyperus rotundus

The mutagenic potential of aqueous, total oligomers flavonoids (TOF), ethyl acetate and methanol extracts from tubers of Cyperus rotundus L. was assessed using Ames Salmonella tester strains TA98 and TA100, and SOS chromotest strain Escherichia coli PQ37 with and without metabolic activation (S9). None of the different extracts produced a mutagenic effect. Likewise, the antimutagenicity of the same extracts was tested using the “Ames test” and the “SOS chromotest”. Our results showed that C. rotundus extracts possess antimutagenic effects against S. typhimurium TA98 and TA100 strains towards the mutagen aflatoxin B1 (AFB1), similar to E. coli PQ37 strain against AFB1 and Nifuroxazide mutagens using the SOS chromotest assay. A free radical scavenging test was used in order to explore the antioxidant capacity of the extracts obtained from the tubers of C. rotundus. TOF, ethyl acetate and methanol extracts showed an important free radical scavenging activity towards the 1,1-diphenyl-2-picrylhydrazine (DPPH) free radical. These extracts showed an IC50 value of respectively 5, 20 and 65?µg?mL^?1. The beneficial effects of TOF, ethyl acetate and methanol extracts of C. rotundus were assessed by antioxidant and antimutagenic activities.     

Antibacterial and antimutagenic activitiy of extracts and essential oil from (Tunisian) Pistacia lentiscus

Aqueous and flavonoid-enriched extract as well as essential oil (EO) obtained from leaves of Pistacia lentiscus were assessed for antibacterial and antimutagenic activities. Antibacterial activity of different extracts and EO were evaluated against six bacterial strains. A marked inhibitory effect was observed against Salmonella typhimurium, whereas lower activity was observed against Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella enteritidis. EO showed significant inhibitory effects against Salmonella typhimurium, Salmonella enteritidis and Staphylococcus aureus. The antimutagenic activity of the different extracts against Aflatoxin B₁ (AFB₁) and sodium azide was demonstrated with the Salmonella typhymurium assay. The number of revertants per plate decreased significantly when the plant extracts were added to the assay system using Salmonella typhimurium TA100, TA98 and TA1535.     

Aliphatic and aromatic halocarbons as potential mutagens in drinking water

Chlorinated phenols are either products of industrial chemical processes or the result of chlorination of drinking water. Often, the formation of chlorinated phenols is based upon naturally occurring phenol. The following chlorinated phenols have been selected for testing in the Ames‐test for their mutagenic activity: 3‐chlorophenol, 4‐chlorophenol, 2,3,6‐, 2,4,5‐, 2,4,6‐trichlorophenol, 4‐chloro‐2‐methylphenol and 4‐chloro‐3‐methylchlorophenol. The tester strains TA97, TA98, TA100 and TA104 were employed. All tested compounds produced mutagenic activity at least in one tester strain. The highest numbers of revertants were detected for 2,3,6‐ and 2,4,6‐trichlorophenol. But in contrast to the other substances, these two induced only frameshift mutations in presence of a metabolizing system. The evidence of their presence in drinking water and of their mutagenic activity makes them to a potential health hazard.     

Mutagenicity of polyaromatic hydrocarbons by chemical models for cytochrome P450 in Ames assay

DNA damage is an important step in carcinogenesis. The Ames assay is a short-term screening of carcinogens that induce DNA damage. Most carcinogens require enzymatic activation through oxidation by cytochrome P450 (CYP450) in the presence of S9 mix. A combination of iron (Fe)(III) porphyrin and an oxidant is also able to oxidize compounds as an alternative metabolic pathway to CYP450. Previously it was reported that a chemical model containing a water-soluble 5,10,15,20-tetrakis(1-methylpyridinium4-yl)porphyrinatoiron(III) chloride (4-MPy) and tert-butyl hydroperoxide (t-BuOOH) activated aromatic amines and amides. In this study, a chemical model composed of an Fe porphyrin, water-insoluble 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinatoiron(III) chloride (F₅P) or water-soluble 4-MPy was optimized with an oxidant – t-BuOOH, magnesium monoperoxyphthalate (MPPT), or iodosylbenzene (PhIO). Subsequently the mutagenicity of benzo[a]pyrene (B[a]P) and chrysene in Salmonella typhimurium TA strains was compared. B[a]P was activated by a combination of F₅P or 4-MPy plus MPPT or PhIO in S. typhimurium TA1538. The B[a]P-induced mutagenicity with F₅P plus oxidant was higher than 4-MPy plus oxidant. Mutagenicity of chrysene, a tetracyclic aromatic hydrocarbon, was not detected in the presence of F₅P/PhIO in S. typhimurium TA98, but was activated in the presence of F₅P/MPPT. The F₅P/MPPT activated other polyaromatic hydrocarbons (PAH) in the S. typhimurium TA98 assay including dibenz[a,c]anthracene, dibenz[a,h]anthracene, 3-methylcholanthrene, and benzo[a]anthracene. The results indicated that the F₅P/MPPT was the most efficient model for detecting PAH-induced mutagenicity in the Ames assay.     

采用生物发光检测法进行Ames试验的研究

将自行构建的含有青海弧菌荧光酶基因的质粒pACYCL184引入Ames试验的4个菌株TA97、TA98、TA100、TA102中,构建成能够生物发光的工程菌,分别命名为TAL97、TAL98、TAL100、TAL102.实验表明,该4株工程菌保持原出发菌株所具有的与Ames试验相关的性状,对各类致突变剂有良好的反应,且可用平皿计数法进行致突变试验.其发光值与致突变剂浓度存在良好的量效关系,故可用发光检测取代原Ames试验的平皿计数,使检测更简单、方便、快速.图3表3参11     

Synthesis and biological activities of new azacrown ether Schiff bases and spectrophotometric studies of their complexation with [60]fullerene

A series of novel azacrown ether Schiff bases 1–3 have been synthesized in good yield and in a simple way. Their host–guest interaction with [60]fullerene has been studied in toluene by absorption spectroscopic method. All the complexes are found to be stable with 1:1 stoichiometry. Because of their potential applications in industry, agriculture and medicine, they were investigated for their mutagenic and antimutagenic activities using the spot test and the plate incorporation assay of Ames. Compounds 1, 2 and 3 were found to be nonmutagenic in the Ames test using strains TA 1535, TA100 and TA97a of Salmonella typhimurium. However, using strain TA102 revealed that, although both compounds 1 and 2 were nonmutagenic, compound 2 gave a positive response indicating that it acts as an oxidative mutagen. The structure-activity relationship may throw some light on the biological activity of such series of compounds.     

Evaluation of mutagenicity associated with Escherichia coli inactivation in UV-treated orange juice

UV radiation is an alternative technology for the elimination of pathogenic micro-organisms in liquid food. The objectives of this work were to investigate mutagenesis using the Ames test in : (1) fresh squeezed orange juice submitted to UV radiation doses required to achieve 5 and 10 log₁₀ reductions of different strains of Escherichia coli serotype O157:H7 at two temperatures, and (2) commercial pasteurized orange juice submitted to thermal treatment.

Two histidine-auxotrophic strains, Salmonella Typhimurium TA98 and TA97a, were used in the Ames test with and without metabolic activation.

In commercial pasteurized orange juices, mutagenesis was not observed with S. Typhimurium TA98 strain with and without metabolic activation, but high mutagenic effect was observed using TA97a with metabolic activation.

UV radiation did not affect the stability of ascorbic acid in aqueous solution. However, degradation of ascorbic acid was observed when UV treatment was performed on squeezed orange juice, following first order kinetics.

UV treatment required to achieve 5 log₁₀ reductions (1.5 J/cm²) did not show a mutagenic effect with and without metabolic activation using the tested strains, but a higher UV radiation dose necessary to produce 10 log₁₀ reductions (3.0 J/cm²) showed mutagenicity with metabolic activation.     

Silver nanoparticle antimicrobial activity explained by membrane rupture and reactive oxygen generation

Silver nanoparticles are widely used as antimicrobial compounds based on empirical observations. However, there is few knowledge on the mechanism ruling the antimicrobial activity and toxicity of Ag nanoparticles. Here, we investigated this mechanism. Nano-Ag was synthesised by thermal co-reduction. Mutagenicity analysis was performed using Salmonella typhimurium histidine auxotrophic strains TA 98 and TA 100 at nano-silver concentrations of 100 to 500 µg per plate. Dose-dependent analysis for reactive oxygen species generation has been performed using 2,7-dichlorofluorescein diacetate dye. Membrane integrity has been analyzed at 260 nm, before and after treatment. We also used scanning electron microscopy, membrane permeabilization test, and superoxide formation determinations. Results show that the average particle size of Ag nanoparticle is 60.4 ± 3.8 nm. The minimum inhibitory concentration of Ag nanoparticles for E.coli is 30 µg/mL; the minimum bactericidal concentration is 40 µg/mL. Ames mutagenicity tests showed negative results, which may be explained by the antimicrobial activity of nano-silver. Bacterial inner wall were indeed ruptured, and cytoplasmic content was released after 5 min of treatment in a dose-dependent manner. We thus propose that reactive oxygen generation and alteration of membrane integrity and permeability are the major mechanism of antimicrobial activity of nano-silver.     

2-硝基芴的致突变性受共存多环芳烃的影响

本文以Ames试验的TA_(98)菌株研究了2-硝基芴(2-Nitroflurene)在其它多环芳烃共存时,其致突变性的变化.结果显示:它与其它硝基多环芳烃共存时.直接致突变性增强;而与其它无直接致突变性的多环芳烃共存时,其直接致突变性减弱,且多环芳烃的环数越多、减弱作用越强,这可能是因为硝基多环芳烃具有亲电子性,DNA的碱基有亲核性,易于结合,造成DNA的损伤;而多环芳烃一般具有供电子性,阻碍了硝基多环芳烃与DNA碱基的结合.     

Genotoxic potential of organic extracts from municipal reclaimed water in Tianjin,China

Despite increasing pressure to make more efficient use of water resources, the widespread use of reclaimed water still remains a contentious issue, primarily because of risks to human health arising from water pollution by organic compounds. Therefore, safety evaluation of reclaimed water is an urgent need. The aim of this study was to determine the genotoxic potential of reclaimed water during low and high water periods. Reverse phase C-18 solid-phase extraction (RP-C18SPE) was used for the extraction of organic compounds from water samples. The tests, namely, Ames, micronucleus and chromosome aberrations were used to determine the damage caused by water samples on genetic material. Ames tests showed that both influent and effluent reclaimed water, except influent after metabolism by S9 in high water period, induced mutation of TA98 and TA100 strains of Salmonella typhimurium in a concentration-response manner. There were no significant differences in micronucleus and chromosome aberration tests. Even after treatment, reclaimed water in Tianjin still showed mutational effects and new strategies for reduction of genotoxins need to be considered.     

Evaluation of genotoxic potential of industrial waste contaminated soil extracts of Amritsar, India

The rapid increase in population together with unplanned disposal of effluents from various industries has resulted in accumulation of various heavy metals like As, Cr, Cu, Hg, Ni, Pb and Zn in soil ecosystem which ultimately causes DNA damage in living systems. Considering this, the present study was designed to evaluate the content of various heavy metals (Cu, Cr, Co, Hg, Mn, Ni, Zn) and genotoxicity/mutagenicity of soil samples collected from the outskirts of two industries viz. zinc coating industry (SI) and copper sulphate manufacturing industry (SII) employing Allium root anaphase aberration assay (A/RAAA) and Ames assay. The physicochemical parameters like bulk density, water holding capacity, moisture content, pH, nitrates, phosphates and potassium were also estimated. It was observed that SI sample contained Ni (6.86 mg g-1), Zn (6.53 mg g-1), Co (5.05 mg g-1) and Cr (4.49 mg g-1), while SII contained Cu (32.86 mg g-1), Ni (9.66 mg g-1), Co (6.85 mg g-1) and Zn (5.41 mg g-1). In A/RAA assay, the percentage of cells with anaphase aberrations ranged from 3.63 to 10.67 and 0.38 to 4.83% for samples SI and SII, respectively. In Ames test, sample SII was found to be lethal to Salmonella tester strains at all concentrations used, while sample SI was found to be mutagenic in TA100 strains of Salmonella typhimurium. Sample SII was found to be strongly acidic with pH 3.46. The present study focuses on the increasing heavy metal pollution in Amritsar city due to industrial discharges over lands and also infers that both bioassays Ames and A/RAAA can serve as first alert indication of pollution.     

Investigating the potential for different scooter and car exhaust emissions to cause cytotoxic and (pro-)inflammatory responses to a 3D in vitro model of the human epithelial airway

The aim of this study was to compare the cytotoxicity and the (pro-)inflammatory responses of two-stroke (direct injection and carburetor technology) and four-stroke scooter and diesel car exhaust emissions on lung cells in vitro. This was analyzed by exposing a 3D in vitro model of the epithelial airway (consisting of human bronchial epithelial cells (cell line 16HBE14o^?) combined with human whole blood monocyte-derived macrophages and dendritic cells) to physically characterized exhaust emissions. Biological endpoints of cytotoxicity (lactate dehydrogenase release), as well as pro-inflammatory cytokine (tumor necrosis factor (TNF)-α) and inflammatory chemokine (interleukin(IL)-8) stimulation were examined. Two-stroke direct injection scooter exhaust contained the highest particle number concentration and nitrogen oxides (NO _x ) concentrations and the emissions from the two-stroke carburetor scooter contained the highest hydrocarbon and lowest NO _x concentrations. The four-stroke scooter emitted the highest carbon monoxide concentration whereas the cars emitted the lowest. The combination of various technical optimizations for the two-stroke direct injection scooter (particle filter, oxidative catalyst, better oil and fuel) reduced the total emissions strongly and the TNF-α concentration significantly (p?相似文献   

Genotoxicity,antifungal and antibacterial activity of newly synthesized N-(3-phthalidyl)amines and o-benzoyl benzamide derivatives

A number of newly synthesized phthalidylamines and o-benzoylbenzamide derivatives were evaluated for some biological activities. Synthesis was established by condensation of 3-acetoxyphthalide 1 with morpholine, piperidine, N,N-diisobutyl-N,N-dibenzylamines and piperazine, which afforded N-(3-phthalidyl)amines 3a–d, and 4 respectively, while with N,N-diisopropylamine, o-formyl-N,N-diisopropyl benzamide 5a is formed exclusively. On the other hand, the reaction of 3-acetoxy-3-phenylphthalide 2 with secondary amines afforded o-benzoylbenzamide derivatives 5b–c, 6 in a high yield. The structure of the reaction products was established from their spectral data. These products were screened for antifungal, antibacterial and genotoxic effect. It was found that all tested compounds have antifungal activity. Compounds 1, 2, 3d and 5b were found to be active against Escherichia coli, Bacillus subtilis and Staphylococcus aureus. Genotoxic effects using Ames test showed that Compounds 1 and 2 have a weak base-pair substitution mutagenicity while a clear base-pair substitution mutagenic activity was shown by 3a using TA100-strain of Salmonella typhimurium. Compound 4 showed a frameshift mutgenicity while a weak oxidative mutagenic action was revealed by 6. No change on the mutagenicity of the tested chemicals was observed after using the S9 metabolic activation system.     

Model reactions of chromium compounds with mammalian and bacterial cells†

Chromate uptake, reduction, cytotoxicity and mutagenicity were studied with human red blood cells, Chinese hamster ovary (CHO) cells and/or Salmonella typhimurium mutant cells. All cell types rapidly took up chromates whereas chromium(III) salts were excluded under the experimental conditions. Red blood cells reduced and accumulated chromium from chromate. At concentrations above 0.1 mM, chromate inactivated the red cell chromate carrier. Chromate above 0.01 mM inhibited CHO cell proliferation irrespective of the cations present. Chromate and two chromium(III) complexes were mutagenic with Salmonella mutants in the Ames’ assay. A model for chromate metabolism and genotoxicity is proposed.