Principles for assessing the genotoxicity of carbon nanomaterials in vitro (on the example of carbon nanotubes) (literature review)

2021 ◽  
Vol 29 (6) ◽  
pp. 16-23
Author(s):  
Gulnaz Faezovna Gabidinova ◽  
Gyuzel Abdulkhalimovna Timerbulatova ◽  
Liliya Minvagizovna Fatkhutdinova
Keyword(s):  
Carbon Nanomaterials ◽  
Physicochemical Characterization ◽  
Gene Mutations ◽  
Micronucleus Assay ◽  
Bibliographic Databases ◽  
Chromosomal Damage ◽  
Colorimetric Test ◽  
Wide Range ◽  
Dna Strand

Introduction. Genotoxicity of nanomaterials (NM) is becoming a major concern when investigating new NM for their safety. Each mutagen is considered to be potentially carcinogenic, therefore a genotoxicity assessment is necessary. However, a clear strategy for assessing the genotoxic effect of NM has not yet been developed. Material and methods. The material for the analysis have included literature sources from the bibliographic databases PubMed, Scopus, RSCI. Results. Physicochemical characterization of NM is carried out using high-resolution microscopic and light scattering methods. Before testing for genotoxicity, it is necessary to know the cytotoxicity of the tested NM in order to select the appropriate concentration range. The most important and significant tests are based on the cell viability. MTT assay is a colorimetric test that evaluates the metabolic activity of cells. In addition, viability can be determined using microscopy, flow cytometry, determination of lactate dehydrogenase. Genotoxicity evaluation can be carried out only after the preliminary steps. The strategy should include genotoxicity endpoints: DNA damage, gene mutations, chromosomal damage. The in vitro mammalian gene mutation test, usually performed using mouse lymphoma cells, detects a wide range of genetic damage, including gene deletions. The most common test for detecting chromosomal damage is an in vitro micronucleus assay. DNA strand breaks are most often assessed using the comet DNA assay. Conclusion. Compulsory stages in the study of the genotoxicity of nanomaterials should be preliminary studies, including physicochemical characterization and assessment of cytotoxicity, as well as the study of the endpoints of genotoxicity and potential mechanisms.

scholarly journals Role of Surface Chemistry in the In Vitro Lung Response to Nanofibrillated Cellulose

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 389
Author(s):  
Kukka Aimonen ◽  
Satu Suhonen ◽  
Mira Hartikainen ◽  
Viviana R. Lopes ◽  
Hannu Norppa ◽  
...  
Keyword(s):  
Micronucleus Assay ◽  
Nanofibrillated Cellulose ◽  
In Vitro Toxicity ◽  
Surface Functional Group ◽  
Fiber Morphology ◽  
Surface Charges ◽  
Cell Viability Assay ◽  
Wide Range ◽  
Group Density

Wood-derived nanofibrillated cellulose (NFC) has emerged as a sustainable material with a wide range of applications and increasing presence in the market. Surface charges are introduced during the preparation of NFC to facilitate the defibrillation process, which may also alter the toxicological properties of NFC. In the present study, we examined the in vitro toxicity of NFCs with five surface chemistries: nonfunctionalized, carboxymethylated, phosphorylated, sulfoethylated, and hydroxypropyltrimethylammonium-substituted. The NFC samples were characterized for surface functional group density, surface charge, and fiber morphology. Fibril aggregates predominated in the nonfunctionalized NFC, while individual nanofibrils were observed in the functionalized NFCs. Differences in surface group density among the functionalized NFCs were reflected in the fiber thickness of these samples. In human bronchial epithelial (BEAS-2B) cells, all NFCs showed low cytotoxicity (CellTiter-GloVR luminescent cell viability assay) which never exceeded 10% at any exposure time. None of the NFCs induced genotoxic effects, as evaluated by the alkaline comet assay and the cytokinesis-block micronucleus assay. The nonfunctionalized and carboxymethylated NFCs were able to increase intracellular reactive oxygen species (ROS) formation (chloromethyl derivative of 2′,7′-dichlorodihydrofluorescein diacetate assay). However, ROS induction did not result in increased DNA or chromosome damage.

scholarly journals Protective Activity of C-Geranylflavonoid Analogs from Paulownia tomentosa against DNA Damage in 137Cs Irradiated AHH-1Cells

2014 ◽  
Vol 9 (9) ◽  
pp. 1934578X1400900
Author(s):  
Hyung-In Moon ◽  
Min Ho Jeong ◽  
Wol Soon Jo
Keyword(s):  
Dna Damage ◽  
Protective Effects ◽  
Strand Breaks ◽  
Human Lymphoblastoid Cell ◽  
Wide Range ◽  
Radiation Induced ◽  
Anti Oxidant ◽  
Dna Strand ◽  
Cellular Dna

Radiotherapy is an important form of treatment for a wide range of cancers, but it can damage DNA and cause adverse effects. We investigated if the diplacone analogs of P. tomentosa were radio-protective in a human lymphoblastoid cell line (AHH-1). Four geranylated flavonoids, diplacone, 3′- O-methyl-5′-hydroxydiplacone, 3′- O-methyl-5′- O-methyldiplacone and 3′- O-methyldiplacol, were tested for their antioxidant and radio-protective effects. Diplacone analogs effectively scavenged free radicals and inhibited radiation-induced DNA strand breaks in vitro. They significantly decreased levels of reactive oxygen species and cellular DNA damage in 2 Gy-irradiated AHH-1 cells. Glutathione levels and superoxide dismutase activity in irradiated AHH-1 cells increased significantly after treatment with these analogs. The enhanced biological anti-oxidant activity and radioprotective activity of diplacone analogs maintained the survival of irradiated AHH-1 cells in a clonogenic assay. These data suggest that diplacone analogs may protect healthy tissue surrounding tumor cells during radiotherapy to ensure better control of radiotherapy and allow higher doses of radiotherapy to be employed.

scholarly journals Inclusion Complexes of β and HPβ-Cyclodextrin with α, β Amyrin and In Vitro Anti-Inflammatory Activity

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 241 ◽  
Author(s):  
Walter Ferreira da Silva Júnior ◽  
Danielle Lima Bezerra de Menezes ◽  
Luana Carvalho de Oliveira ◽  
Letícia Scherer Koester ◽  
Patrícia Danielle Oliveira de Almeida ◽  
...  
Keyword(s):  
Inclusion Complexes ◽  
Biological Activities ◽  
Physicochemical Characterization ◽  
Inflammatory Activity ◽  
Scanning Calorimetry ◽  
Promising Alternative ◽  
Wide Range ◽  
Natural Mixture ◽  
Anti Inflammatory

α, β amyrin (ABAM) is a natural mixture of pentacyclic triterpenes that has a wide range of biological activities. ABAM is isolated from the species of the Burseraceae family, in which the species Protium is commonly found in the Amazon region of Brazil. The aim of this work was to develop inclusion complexes (ICs) of ABAM and β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) by physical mixing (PM) and kneading (KN) methods. Interactions between ABAM and the CD’s as well as the formation of ICs were confirmed by physicochemical characterization in the solid state by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetry (TG) and differential scanning calorimetry (DSC). Physicochemical characterization indicated the formation of ICs with both βCD and HPβCD. Such ICs were able to induce changes in the physicochemical properties of ABAM. In addition, the formation of ICs with cyclodextrins showed to be an effective and promising alternative to enhance the anti-inflammatory activity and safety of ABAM.

scholarly journals The CREB-binding protein inhibitor ICG-001: a promising therapeutic strategy in sporadic meningioma with NF2 mutations

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Jiaojiao Deng ◽  
Lingyang Hua ◽  
Tao Han ◽  
Mi Tian ◽  
Daijun Wang ◽  
...  
Keyword(s):  
Binding Protein ◽  
Gene Mutations ◽  
Therapeutic Effects ◽  
Creb Binding Protein ◽  
Cycle Arrest ◽  
Large Patient ◽  
Wide Range ◽  
Patient Series ◽  
Responsive Element

Abstract Background Meningiomas with Neurofibromin 2 gene mutations (NF2-mutant meningiomas) account for ~40% of the sporadic meningiomas. However, there is still no effective drug treatment for the disease. Methods Expression profile of Merlin protein was explored through immunohistochemistry in a meningioma patient cohort (n = 346). A 20-agent library covering a wide range of meningioma relevant targets was tested using meningioma cell lines IOMM-Lee (NF2 wildtype) and CH157-MN (NF2 deficient). Therapeutic effects and biological mechanisms of the identified compound, ICG-001, in NF2-mutant meningiomas were further characterized in vitro and in patient-derived xenograft (PDX) models. Results Low Merlin expression was associated with meningioma proliferation and poor clinical outcomes in a large patient series. ICG-001, a cAMP-responsive element binding (CREB)-binding protein (CBP) inhibitor, selectively suppressed tumor growth of cells with low Merlin expression. Besides, ICG-001 mediated CH157-MN and IOMM-Lee growth inhibition primarily through robust induction of the G1 cell-cycle arrest. Treatment with ICG-001 alone significantly reduced the growth of NF2-mutant xenografts in mice, as well. We also provide further evidence that ICG-001 inhibits proliferation of NF2-mutant meningioma cells at least partly through attenuating the FOXM1-mediated Wnt/β-catenin signaling. Conclusions This study highlights the importance of ligand-mediated Wnt/β-catenin signaling as well as its drugable potency in NF2-mutant meningioma.

scholarly journals In Vitro Analysis of the Effects of ITER-Like Tungsten Nanoparticles: Cytotoxicity and Epigenotoxicity in BEAS-2B Cells

Nanomaterials ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 1233 ◽  
Author(s):  
Chiara Uboldi ◽  
Marcos Sanles Sobrido ◽  
Elodie Bernard ◽  
Virginie Tassistro ◽  
Nathalie Herlin-Boime ◽  
...  
Keyword(s):  
Synthesis Method ◽  
Micronucleus Assay ◽  
Strand Breaks ◽  
Plasma Sputtering ◽  
Dna Strand ◽  
Vitro Analysis ◽  
Tungsten Nanoparticles ◽  
Experimental Fusion ◽  
In Vitro Analysis

Tungsten was chosen as a wall component to interact with the plasma generated by the International Thermonuclear Experimental fusion Reactor (ITER). Nevertheless, during plasma operation tritiated tungsten nanoparticles (W-NPs) will be formed and potentially released into the environment following a Loss-Of-Vacuum-Accident, causing occupational or accidental exposure. We therefore investigated, in the bronchial human-derived BEAS-2B cell line, the cytotoxic and epigenotoxic effects of two types of ITER-like W-NPs (plasma sputtering or laser ablation), in their pristine, hydrogenated, and tritiated forms. Long exposures (24 h) induced significant cytotoxicity, especially for the hydrogenated ones. Plasma W-NPs impaired cytostasis more severely than the laser ones and both types and forms of W-NPs induced significant micronuclei formation, as shown by cytokinesis-block micronucleus assay. Single DNA strand breaks, potentially triggered by oxidative stress, occurred upon exposure to W-NPs and independently of their form, as observed by alkaline comet assay. After 24 h it was shown that more than 50% of W was dissolved via oxidative dissolution. Overall, our results indicate that W-NPs can affect the in vitro viability of BEAS-2B cells and induce epigenotoxic alterations. We could not observe significant differences between plasma and laser W-NPs so their toxicity might not be triggered by the synthesis method.

DT-Diaphorase Affects the Mutagenic Activity of Pyrene 1,6-Quinone in Chinese Hamster Epithelial Liver (CHEL) Cells

1996 ◽  
Vol 24 (4) ◽  
pp. 567-571
Author(s):  
Paola Rossini ◽  
Gino Turchi
Keyword(s):  
Mutagenic Activity ◽  
Chinese Hamster ◽  
Gene Mutations ◽  
Specific Pattern ◽  
V79 Cells ◽  
Mutagenic Potential ◽  
Mammalian Cell Lines ◽  
Wide Range ◽  
Dt Diaphorase

The mutagenic potential of pyrene 1,6-quinone (P 1,6-Q) has been studied in a wide range of in vitro genetic assays including the use of mammalian cell lines. P 1,6-Q has been shown to induce gene mutations and micronuclei in V79 cells, whereas, in Chinese hamster epithelial liver (CHEL) cells, a cell line which retains activities of various xenobiotic-metabolising enzymes, a non-specific pattern of structural and numerical chromosomal aberrations has been observed. In this study, we have evaluated the mutagenic activity of P 1,6-Q on V79 and CHEL cells both with and without dicoumarol, a potent inhibitor of DT-diaphorase. In V79 cells, dicoumarol (100μM) did not affect the mutagenic response, whereas in CHEL cells, the mutation frequency significantly increased. This suggests that DT-diaphorase, which is expressed in liver cells at high levels, has a possible role in the detoxification of P 1,6-Q to redox-stable hydroquinone.

The Relevance of Photomutagenicity Testing as a Predictor of Photocarcinogenicity

1998 ◽  
Vol 17 (5) ◽  
pp. 551-558 ◽  
Author(s):  
Lutz Müller ◽  
Peter Kasper
Keyword(s):  
Oxidative Damage ◽  
Mammalian Cells ◽  
Active Oxygen Species ◽  
Gene Mutations ◽  
Oxygen Species ◽  
Chromosomal Damage ◽  
Hairless Mice ◽  
Molecular Events ◽  
Repair Mechanisms

Today's lifestyle is associated with frequent and intense exposure to ultraviolet radiation (UVR). The tumorigenic effects of UVR are well known. Specifically, the premutagenic lesions of UVB (290-320 nm) are known to be the most important molecular events in UVR tumorigenicity. The less carcinogenic UVA (320-400 nm) mainly generates oxidative damage in the DNA via photody-namic generation of active oxygen species involving endogenous or exogenous photosen sitizers. Several pharmaceuticals are known to act as photosensitizers. Photoinstable phenothiazines, furocoumarins, and fluoroquinolones were shown to be very efficient inducers of chromosomal damage in mammalian cells in culture. Photocar cinogenicity testing in hairless mice of furocoumarins and several fluoroquinolones demonstrated a higher incidence and a shorter latent period for skin tumors compared to UVR alone. These data show a good correlation between the photomutagenic and photocarcinogenic potential of these compounds. Although mammalian cells possess effective repair mechanisms for oxidative damage, photoproducts, and dimers, these repair mechanisms can be overloaded. Eventually, unrepaired damage leads to gene mutations or chromosomal damage in exposed cells and to tumors in the skin. Therefore, in vitro photomutageni-city testing in mammalian cells may be an early and easy-to-measure predictor of the photocarcinogenic potential of a pharmaceutical.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

In Vitro Clot Lysis as a Potential Indicator of Thrombus Resistance to Fibrinolysis – Study in Healthy Subjects and Correlation with Blood Fibrinolytic Parameters

1997 ◽  
Vol 77 (04) ◽  
pp. 725-729 ◽  
Author(s):  
Mario Colucci ◽  
Silvia Scopece ◽  
Antonio V Gelato ◽  
Donato Dimonte ◽  
Nicola Semeraro
Keyword(s):  
Plasminogen Activator ◽  
Clot Lysis ◽  
Individual Response ◽  
Plasminogen Activator Inhibitor 1 ◽  
Autologous Plasma ◽  
Wide Range ◽  
Blood Clots ◽  
Physiological Variations ◽  
Pai 1

SummaryUsing an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in 103 healthy donors. 125I-fibrin labelled blood clots were submersed in autologous plasma, supplemented with 500 ng/ml of rt-PA or solvent, and the degree of lysis was determined after 3 h of incubation at 37° C. Baseline plasma levels of t-PA, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-anti-plasmin, fibrinogen, lipoprotein (a), thrombomodulin and von Willebrand factor as well as platelet and leukocyte count and clot retraction were also determined in each donor. rt-PA-induced clot lysis varied over a wide range (28-75%) and was significantly related to endogenous t-PA, PAI-1, plasminogen (p <0.001) and age (p <0.01). Multivariate analysis indicated that both PAI-1 antigen and plasminogen independently predicted low response to rt-PA. Surprisingly, however, not only PAI-1 but also plasminogen was negatively correlated with rt-PA-ginduced clot lysis. The observation that neutralization of PAI-1 by specific antibodies, both in plasma and within the clot, did not potentiate clot lysis indicates that the inhibitor, including the platelet-derived form, is insufficient to attenuate the thrombolytic activity of a pharmacological concentration of rt-PA and that its elevation, similarly to the elevation of plasminogen, is not the cause of clot resistance but rather a coincident finding. It is concluded that the in vitro response of blood clots to rt-PA is poorly influenced by the physiological variations of the examined parameters and that factors other than those evaluated in this study interfere with clot dissolution by rt-PA. In vitro clot lysis test might help to identify patients who may be resistant to thrombolytic therapy.

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