Plants from Northwestern Anatolia Display Selective Cytotoxicity and Induce Mitotic Catastrophe: A Study on Anticancer and Genotoxic Activities

Anatolia is rich in floristic diversity with a high rate of endemism. Eight plant species from northwestern Anatolia were evaluated for their anti-growth properties in two malignant (MCF-7 and MDA-MB-231) and a non-malignant (MCF-10A) breast cell lines. The two most active extracts, Achillea multifida (AME) and Astragalus sibthorpianus (ASE), induced apoptotic cell death in all cell lines. The major phenolic compounds in AME were identified as chlorogenic acid, and catechins in ASE. ASE displayed selective cytotoxicity against breast cancer cells, with DNA damage repair in non-malignant cells contributing to its selectivity. Conversely, AME induced DNA damage in a time-dependent manner and displayed a dual dose-dependent biological activity, resulting in mitotic catastrophe and apoptosis at different doses. Most plant species exhibited moderate to strong cytotoxicity, highlighting their medicinal and economic potential and the need for their protection.     

Synthesis and Evaluation of Water‐Soluble 2‐Aryl‐1‐Sulfonylpyrrolidine Derivatives as Bacterial Biofilm Formation Inhibitors

The approach to the novel 1‐[(2‐aminoethyl)sulfonyl]‐2‐arylpyrrolidines via unique intramolecular cyclization/aza‐Michael reactions of N‐(4,4‐diethoxybutyl)ethenesulfonamide have been developed, which benefits from high yields of target compounds, mild reaction conditions, usage of inexpensive and low‐toxic reagents, and allows for wide variability in both amine and aryl moieties. Biotesting with whole‐cell luminescent bacterial biosensors responding to DNA damage showed that all tested compounds are not genotoxic. Tested compounds differently affect the formation of biofilms by Vibrio aquamarinus DSM 26054. Some of the tested compounds were found to suppress the bacterial biofilms growth and thus are promising candidates for further studies.     

Genotoxic evaluation of the antimicrobial drug, trimethoprim, in cultured human lymphocytes

The antimicrobial drug, trimethoprim, was evaluated for genotoxicity in human peripheral blood lymphocyte cultures set-up from two healthy donors. Sister-chromatid exchanges (SCE) and micronuclei (MN) were scored as genetic endpoints. The treatment was done using different trimethoprim concentrations ranging from 1 to 100 μg/ml. From our results, we can conclude that this drug is able to induce both cytotoxic and moderate genotoxic effects, as revealed by the increases seen in SCE and MN frequencies in cultures from the two donors and, at least, at one of the concentrations tested.     

Impact of α‐hydroxy‐propanodeoxyguanine adducts on DNA duplex energetics: Opposite base modulation and implications for mutagenicity and genotoxicity

Acrolein is an α,β‐unsaturated aldehyde that is a major environmental pollutant, as well as a product of cellular metabolism. DNA bases react with acrolein to form two regioisomeric exocyclic guanine adducts, namely γ‐hydroxy‐propanodeoxyguanosine (γ‐OH‐PdG) and its positional isomer α‐hydroxy‐propanodeoxyguanosine (α‐OH‐PdG). The γ‐OH‐PdG isomer adopts a ring‐opened conformation with minimal structural perturbation of the DNA host duplex. Conversely, the α‐OH‐PdG isomer assumes a ring‐closed conformation that significantly disrupts Watson‐Crick base‐pair alignments within the immediate vicinity of the damaged site. We have employed a combination of calorimetric and spectroscopic techniques to characterize the thermodynamic origins of these lesion‐induced structural alterations. Specifically, we have assessed the energetic impact of α‐OH‐PdG centered within an 11‐mer duplex by hybridizing the adduct‐containing oligonucleotide with its complementary strand harboring a central base N [where N = C or A], yielding a pair of duplexes containing the nascent lesion (α‐OH‐PdG·C) or mismatched adduct (α‐OH‐PdG·A), respectively. Our data reveal that the nascent lesion is highly destabilizing, whereas its mismatched counterpart partially ameliorates α‐OH‐PdG‐induced destabilization. Collectively, our data provide energetic characterizations of the driving forces that modulate error‐free versus error‐prone DNA translesion synthesis. The biological implications of our findings are discussed in terms of energetically probing acrolein‐mediated mutagenicity versus adduct‐induced genotoxicity. © 2009 Wiley Periodicals, Inc. Biopolymers 93: 370–382, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com     

Detection of genotoxicity of metallic compounds by the bacterial bioluminescence test

Twenty metallic compounds were assayed for their genotoxic mutagenic activity by the bioluminescence test restoration of the luminescence of dark mutant of the luminous bacterium Photobacterium fischeri). The activity of the metals was tested in a liquid medium as well as on a solid medium. K₂Cr₂O₇, MnCl₂, BeCl₂, KH₂AsO₄, ZnCl₂ and Na₂WO₄ showed strong activity in liquid medium while AgNO₃, Cd(OOCCH₃)₂, CoCl₂, CuCl₂, HgCl₂, Na₂SeO₃ and Pb(NO₃)₂ were more active in the solid medium test. BaCl₂, Na₂MoO₄, NaAsO₂, NiSO₄, Na₂SeO₄, RbCl, and SnCl₂ were not active in the bioluminescence test. The correlation between the genotoxic activity of the tested metallic compounds in the bioluminescence test and other bacterial tests for genotoxic agents as well as the correlation between these results and the carcinogenicity of these compounds is discussed.     

Genotoxic evaluation of the River Paranaíba hydrographic basin in Monte Carmelo,MG, Brazil,by the Tradescantia micronucleus

Pollutants have adverse effects on human health and on other organisms that inhabit or use water resources. The aim of the present study was to assess the environmental quality of three watercourses in Monte Carmelo, MG, Brazil, using the micronucleus test on Tradescantia. For each treatment, 15 plants were exposed to water samples for 24 h. The control group was exposed to formaldehyde (0.2%) and the negative control to Hoagland solution. Subsequently the plants were placed in Hoagland solution for 24 h to recover. Cells were stained with 2% acetic carmine and examined by light microscopy. Three hundred tetrads were analyzed per slide. The frequency of genotoxic alterations was expressed as the number of micronuclei per 100 tetrads, and the groups were compared by ANOVA. At all sample sites for each watercourse significant genotoxicity indices were observed. The results suggest that in the Mumbuca creek, the current situation of effluent discharge should be reconsidered by the municipal environmental authorities. The increase in micronucleus frequency denoted for water samples of the Mumbuca creek, Lambari river and Perdizes river emphasizes the need to adopt environmental vigilance strategies, such as biological monitoring.     

In Vitro Genotoxic and Antigenotoxic Effects of Ten Novel Synthesized 4-Thiazolidinone Derivatives

Heterocyclic compounds are found in a variety of drug molecules, and bioactive natural products. 4-Thiazolidinones (4-TZDs), which represent an important class of heterocyclic compounds, are of great interest today with their diverse bioactivities. In this study, ten novel 4-TZD derivatives ( C1 – C10 ) were synthesized, characterized by spectroscopic techniques, and their genotoxic, and antigenotoxic properties were investigated in vitro using the Ames Salmonella/microsome mutagenicity assay in the concentration range of 0.2–1.0 mM/plate. The results revealed that none of the compounds were mutagenic on the three different Salmonella typhimurium strains up to the highest concentration tested. Furthermore, in our study, C1 , C4 , C6 , and C9 showed significant, ranging from moderate to strong, antigenotoxic effects against mutagen-induced DNA damage at relatively higher doses. Among these, C4 had the best potential to inhibit the number of revertant colonies induced by 9-aminoacridine (9-AA), with a maximum inhibition rate of 47.9 % for 1.0 mM/plate. As a result, preliminary knowledge about the safety of the use of ten novel synthesized 4-TZD compounds likely to exhibit many bioactivities was obtained in this study. In addition, the significant in vitro antimutagenic activity of some derivatives increases the importance of studies for the development of new pharmacological agents for cancer prevention.     

Genotoxic potential of the latex from cotton-leaf physicnut (Jatropha gossypiifolia L.)

Jatropha gossypiifolia L. (Euphorbiaceae), popularly known as cotton-leaf physicnut, is a milky shrub notable for its medicinal properties. The present study aimed to evaluate the toxic, cytotoxic and genotoxic effects of the latex of J. gossypiifolia, using Allium cepa L. as test system. Seeds of A. cepa were exposed to five concentrations of the latex (1.25; 2.5; 5; 10 and 20 mL/L) in order to evaluate parameters of toxicity (evaluation of root growth), cytotoxicity (mitotic index frequency) and genotoxicity (frequency of chromosome alterations). The latex showed a significant decrease in root mean growth value as well as mitotic index for the tested concentrations, except for 1.25 mL/L, when compared to results from the negative control. The 1.25, 2.5 and 5 mL/L concentrations induced significant chromo-some adherences, C-metaphases and/or chromosome bridges, as genotoxic effects. The significant frequency of chromosome bridges also indicated mutagenic potential for chromosomes of J. gossypiifolia as discussed in the paper. Considering that the latex is used in popular therapies, and that the test system A. cepa presents good correlation with tests carried out in mammals, it can be pointed out that its use for medicinal purposes may be harmful to human health especially if ingested.     

Choice of template delivery mitigates the genotoxic risk and adverse impact of editing in human hematopoietic stem cells

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