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.

Mutagenic Activity of p-Toluenesulfonhydrazide

1992 ◽  
Vol 8 (6) ◽  
pp. 369-376 ◽  
Author(s):  
David H. Blakey ◽  
Earle R. Nestmann ◽  
Janet M. Bayley ◽  
K. Laurie Maus ◽  
George R. Douglas
Keyword(s):  
Chinese Hamster Ovary ◽  
Mutagenic Activity ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Gene Mutations ◽  
Metabolic Activation ◽  
High Volume ◽  
Ovary Cells

Toluenesulfonhydrazide (TSH) is a high volume production chemical for which there is relatively little toxicological data. In this study, the mutagenic activity of TSH was determined in the Salmonella/mammalian microsome assay and the in vitro chromosomal aberration assay using Chinese hamster ovary cells. TSH induced gene mutations both with and without metabolic activation in the Salmonella/mammalian microsome assay but that it did not induce chromosomal aberrations in Chinese hamster ovary cells. The results of this study indicate that TSH is an in vitro mutagen and should be assessed for in vivo mutagenicity.

scholarly journals Assessment of the Mutagenic Activity of Extracts of Brazilian Propolis in Topical Pharmaceutical Formulations on Mammalian CellsIn VitroandIn Vivo

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Juliana Marques Senedese ◽  
Aline Rafaela Rodrigues ◽  
Michelle Andrade Furtado ◽  
Viviane Dias Faustino ◽  
Andresa A. Berretta ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Mutagenic Activity ◽  
Biological Activities ◽  
Antioxidant Properties ◽  
Test System ◽  
Negative Control ◽  
Continuous Treatment ◽  
Mutagenic Potential ◽  
Topical Formulations

Propolis possesses various biological activities such as antibacterial, antifungal, anti-inflammatory, anesthetic and antioxidant properties. A topically applied product based on Brazilian green propolis was developed for the treatment of burns. For such substance to be used more safely in future clinical applications, the present study evaluated the mutagenic potential of topical formulations supplemented with green propolis extract (1.2, 2.4 and 3.6%) based on the analysis of chromosomal aberrations and of micronuclei. In thein vitrostudies, 3-h pulse (G1phase of the cell cycle) and continuous (20 h) treatments were performed. In thein vivoassessment, the animals were injured on the back and then submitted to acute (24 h), subacute (7 days) and subchronic (30 days) treatments consisting of daily dermal applications of gels containing different concentrations of propolis. Similar frequencies of chromosomal aberrations were observed for cultures submitted to 3-h pulse and continuous treatment with gels containing different propolis concentrations and cultures not submitted to any treatment. However, in the continuous treatment cultures treated with the 3.6% propolis gel presented significantly lower mitotic indices than the negative control. No statistically significant differences in the frequencies of micronuclei were observed between animals treated with gels containing different concentrations of propolis and the negative control for the three treatment times. Under the present conditions, topical formulations containing different concentrations of green propolis used for the treatment of burns showed no mutagenic effect in either test system, but 3.6% propolis gel was found to be cytotoxic in thein vitrotest.

scholarly journals Genotoxic Effects of Etoposide, Bleomycin, and Ethyl Methanesulfonate on Cultured CHO Cells: Analysis by GC-MS/MS and Comet Assay

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Donald H. Atha ◽  
Erdem Coskun ◽  
Onur Erdem ◽  
Alessandro Tona ◽  
Vytas Reipa ◽  
...  
Keyword(s):  
Comet Assay ◽  
Cho Cells ◽  
Chinese Hamster ◽  
Ethyl Methanesulfonate ◽  
Genotoxic Effects ◽  
Strand Breaks ◽  
Mammalian Cell Lines ◽  
Chromatography Tandem Mass Spectrometry ◽  
Wide Range ◽  
Dna Strand

To evaluate methods for analysis of genotoxic effects on mammalian cell lines, we tested the effect of three common genotoxic agents on Chinese hamster ovary (CHO) cells by single-cell gel electrophoresis (comet assay) and gas chromatography-tandem mass spectrometry (GC-MS/MS). Suspension-grown CHO cells were separately incubated with etoposide, bleomycin, and ethyl methanesulfonate and analyzed by an alkaline comet assay and GC-MS/MS. Although DNA strand breaks were detected by the comet assay after treatment with all three agents, GC-MS/MS could only detect DNA nucleobase lesions oxidatively induced by bleomycin. This demonstrates that although GC-MS/MS has limitations in detection of genotoxic effects, it can be used for selected chemical genotoxins that contribute to oxidizing processes. The comet assay, used in combination with GC-MS/MS, can be a more useful approach to screen a wide range of chemical genotoxins as well as to monitor other DNA-damaging factors.

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.

In vitro micronucleus screening of pharmaceutical candidates by flow cytometry in Chinese hamster V79 cells

2010 ◽  
Vol 52 (5) ◽  
pp. 355-362 ◽  
Author(s):  
John Nicolette ◽  
Marilyn Diehl ◽  
Paul Sonders ◽  
Steve Bryce ◽  
Eric Blomme
Keyword(s):  
Flow Cytometry ◽  
Chinese Hamster ◽  
V79 Cells ◽  
Chinese Hamster V79 Cells

Safety Pharmacology and Genotoxicity Evaluation of AVI-4658

2010 ◽  
Vol 29 (2) ◽  
pp. 143-156 ◽  
Author(s):  
Peter Sazani ◽  
Doreen L. Weller ◽  
Stephen B. Shrewsbury
Keyword(s):  
Micronucleus Test ◽  
Gene Mutations ◽  
Exon Skipping ◽  
Dystrophin Gene ◽  
Mouse Bone Marrow ◽  
Mutagenic Potential ◽  
Safety Pharmacology ◽  
Liver Parameters ◽  
Good Laboratory

Duchenne muscular dystrophy (DMD) is caused by dystrophin gene mutations. Restoration of dystrophin by exon skipping was demonstrated with the phosphorodiamidate morpholino oligomers (PMO) class of splice-switching oligomers, in both mouse and dog disease models. The authors report the results of Good Laboratory Practice–compliant safety pharmacology and genotoxicity evaluations of AVI-4658, a PMO under clinical evaluation for DMD. In cynomolgus monkeys, no test article–related effects were seen on cardiovascular, respiratory, global neurological, renal, or liver parameters at the maximum feasible dose (320 mg/kg). Genotoxicity battery showed that AVI-4658 has no genotoxic potential at up to 5000 μg/mL in an in vitro mammalian chromosome aberration test and a bacterial reverse mutation assay. In the mouse bone marrow erythrocyte micronucleus test, a single intravenous injection up to 2000 mg/kg was generally well tolerated and resulted in no mutagenic potential. These results allowed initiation of systemic clinical trials in DMD patients in the United Kingdom.

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.

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