ROS-mediated genotoxicity of asbestos-cement in mammalian lung cells in vitro

Dopp, Elke; Yadav, Santosh Kumar; Ansari, Furquan Ahmad; Bhattacharya, Kunal; Recklinghausen, U. von; Rauen, Ursula; Rödelsperger, K.; Shokouhi, Behnaz; Geh, Stefan; Rahman, Qamar

doi:10.1186/1743-8977-2-9

Cited by 28 publications

(9 citation statements)

References 24 publications

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“…In this context, our findings show that cancer development after chrysotile exposure may be promoted after cytokinesis failure. Chrysotile fibers have been also related to production of reactive oxygen species [ 47 ] and DNA strand breaks [ 21 , 23 , 48 ]. These alterations, together to the generation of aneuploid cells, create a very favorable context to cancer development and show a possible way of how a mineral fiber can interfere with cell behavior and promote cancer-associated abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression

et al. 2016

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Chrysotile, like other types of asbestos, has been associated with mesothelioma, lung cancer and asbestosis. However, the cellular abnormalities induced by these fibers involved in cancer development have not been elucidated yet. Previous works show that chrysotile fibers induce features of cancer cells, such as aneuploidy, multinucleation and multipolar mitosis. In the present study, normal and cancer derived human cell lines were treated with chrysotile and the cellular and molecular mechanisms related to generation of aneuploid cells was elucidated. The first alteration observed was cytokinesis regression, the main cause of multinucleated cells formation and centrosome amplification. The multinucleated cells formed after cytokinesis regression were able to progress through cell cycle and generated aneuploid cells after abnormal mitosis. To understand the process of cytokinesis regression, localization of cytokinetic proteins was investigated. It was observed mislocalization of Anillin, Aurora B, Septin 9 and Alix in the intercellular bridge, and no determination of secondary constriction and abscission sites. Fiber treatment also led to overexpression of genes related to cancer, cytokinesis and cell cycle. The results show that chrysotile fibers induce cellular and molecular alterations in normal and tumor cells that have been related to cancer initiation and progression, and that tetraploidization and aneuploid cell formation are striking events after fiber internalization, which could generate a favorable context to cancer development.

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Section: Discussionmentioning

confidence: 99%

Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression

et al. 2016

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“…Sterilization of nanoparticles were carried out by heating at 120°C for 2 h and then suspended in complete DMEM-F12 medium. Stock solutions (1mg/ml) of nanoparticles were sonicated to ensure the uniform suspension before being diluted with culture medium used for exposure of cells [15] , [41] . Prior using in the experiments, both the nanoparticles were analyzed for the presence of bacterial endotoxin using Limulus Amebocyte Lysate (LAL) test.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were maintained in 5% CO 2 -95% atmosphere under high humidity at 37°C. Prior using in the experiments, cells were assessed for cell viability by trypan blue dye exclusion assay as describe earlier by us [41] and batches showing viability more than 95% were only used in the experiments.…”

Section: Methodsmentioning

confidence: 99%

Ameliorative Effects of Dimetylthiourea and N-Acetylcysteine on Nanoparticles Induced Cyto-Genotoxicity in Human Lung Cancer Cells-A549

et al. 2011

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We study the ameliorative potential of dimetylthiourea (DMTU), an OH• radical trapper and N-acetylcysteine (NAC), a glutathione precursor/H2O2 scavenger against titanium dioxide nanoparticles (TiO2-NPs) and multi-walled carbon nanotubes (MWCNTs) induced cyto-genotoxicity in cultured human lung cancer cells-A549. Cytogenotoxicity was induced by exposing the cells to selected concentrations (10 and 50 µg/ml) of either of TiO2-NPs or MWCNTs for 24 h. Anti-cytogenotoxicity effects of DMTU and NAC were studied in two groups, i.e., treatment of 30 minutes prior to toxic insult (short term exposure), while the other group received DMTU and NAC treatment during nanoparticles exposure, i.e., 24 h (long term exposure). Investigations were carried out for cell viability, generation of reactive oxygen species (ROS), micronuclei (MN), and expression of markers of oxidative stress (HSP27, CYP2E1), genotoxicity (P53) and CYP2E1 dependent n- nitrosodimethylamine-demethylase (NDMA-d) activity. In general, the treatment of both DMTU and NAC was found to be effective significantly against TiO2-NPs and MWCNTs induced cytogenotoxicity in A549 cells. Long-term treatment of DMTU and NAC during toxic insults has shown better prevention than short-term pretreatment. Although, cells responded significantly to both DMTU and NAC, but responses were chemical specific. In part, TiO2-NPs induced toxic responses were mediated through OH• radicals generation and reduction in the antioxidant defense system. While in the case of MWCNTs, adverse effects were primarily due to altering/hampering the enzymatic antioxidant system. Data indicate the applicability of human lung cancer cells-A549 as a pre-screening tool to identify the target specific prophylactic and therapeutic potential of drugs candidate molecules against nanoparticles induced cellular damages.

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“…Exposure of cultured cells to asbestos leads to the formation of oxyradicals and free radicals that damage DNA [4] , [5] , [6] . It has been shown that exposure of cultured cells to chrysotile can cause double strand breaks in DNA after 3 and 24 h [7] , [8] and can also cause intrachromosomal deletions and DNA mutations [9] .…”

Section: Introductionmentioning

confidence: 99%

The Fate of Chrysotile-Induced Multipolar Mitosis and Aneuploid Population in Cultured Lung Cancer Cells

et al. 2011

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Chrysotile is one of the six types of asbestos, and it is the only one that can still be commercialized in many countries. Exposure to other types of asbestos has been associated with serious diseases, such as lung carcinomas and pleural mesotheliomas. The association of chrysotile exposure with disease is controversial. However, in vitro studies show the mutagenic potential of chrysotile, which can induce DNA and cell damage. The present work aimed to analyze alterations in lung small cell carcinoma cultures after 48 h of chrysotile exposure, followed by 2, 4 and 8 days of recovery in fiber-free culture medium. Some alterations, such as aneuploid cell formation, increased number of cells in G2/M phase and cells in multipolar mitosis were observed even after 8 days of recovery. The presence of chrysotile fibers in the cell cultures was detected and cell morphology was observed by laser scanning confocal microscopy. After 4 and 8 days of recovery, only a few chrysotile fragments were present in some cells, and the cellular morphology was similar to that of control cells. Cells transfected with the GFP-tagged α-tubulin plasmid were treated with chrysotile for 24 or 48 h and cells in multipolar mitosis were observed by time-lapse microscopy. Fates of these cells were established: retention in metaphase, cell death, progression through M phase generating more than two daughter cells or cell fusion during telophase or cytokinesis. Some of them were related to the formation of aneuploid cells and cells with abnormal number of centrosomes.

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ROS-mediated genotoxicity of asbestos-cement in mammalian lung cells in vitro

Cited by 28 publications

References 24 publications

Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression

Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression

Ameliorative Effects of Dimetylthiourea and N-Acetylcysteine on Nanoparticles Induced Cyto-Genotoxicity in Human Lung Cancer Cells-A549

The Fate of Chrysotile-Induced Multipolar Mitosis and Aneuploid Population in Cultured Lung Cancer Cells

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