How To Improve the Dosing of Chemicals in High-Throughput in Vitro Mammalian Cell Assays

2019 ◽  
Vol 32 (8) ◽  
pp. 1462-1468 ◽  
Author(s):  
Fabian C. Fischer ◽  
Luise Henneberger ◽  
Rita Schlichting ◽  
Beate I. Escher
Keyword(s):  
Mammalian Cell ◽  
High Throughput ◽  
Cell Assays

Genetic toxicology studies in SALATRIM structured triacylglycerols. 2. Lack of genetic damage in in vitro mammalian cell assays and the in vivo micronucleus assay

1994 ◽  
Vol 42 (2) ◽  
pp. 521-527 ◽  
Author(s):  
Johnnie R. Hayes ◽  
Colette J. Rudd ◽  
Jon C. Mirsalis ◽  
James P. Bakke ◽  
Richard A. Winegar ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
Micronucleus Assay ◽  
Genetic Damage ◽  
Genetic Toxicology ◽  
Cell Assays ◽  
Structured Triacylglycerols

scholarly journals A Strategy for Discovery of Novel Broad-Spectrum Antibacterials Using a High-Throughput Streptococcus pneumoniae Transcription/Translation Screen

2004 ◽  
Vol 9 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Steven D. Pratt ◽  
Caroline A. David ◽  
Candace Black-Schaefer ◽  
Peter J. Dandliker ◽  
Xiaoling Xuei ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
High Throughput ◽  
Broad Spectrum ◽  
Luciferase Activity ◽  
Luciferase Reporter ◽  
In Vitro Toxicity ◽  
Bacterial Cells ◽  
Biochemical Activity ◽  
Cell Assays

The authors report the development of a high-throughput screen for inhibitors of Streptococcus pneumoniae transcription and translation (TT) using a luciferase reporter, and the secondary assays used to determine the biochemical spectrum of activity and bacterial specificity. More than 220,000 compounds were screened in mixtures of 10 compounds per well, with 10,000 picks selected for further study. False-positive hits from inhibition of luciferase activity were an extremely common artifact. After filtering luciferase inhibitors and several known classes of antibiotics, approximately 50 hits remained. These compounds were examined for their ability to inhibit Escherichia coli TT, uncoupled S. pneumoniae translation or transcription, rabbit reticulocyte translation, and in vitro toxicity in human and bacterial cells. One of these compounds had the desired profile of broad-spectrum biochemical activity in bacteria and selectivity versus mammalian biochemical and whole-cell assays. ( Journal of Biomolecular Screening 2004:3-11)

scholarly journals Development and validation of a high-throughput transcriptomic biomarker to address 21st century genetic toxicology needs

2017 ◽  
Vol 114 (51) ◽  
pp. E10881-E10889 ◽  
Author(s):  
Heng-Hong Li ◽  
Renxiang Chen ◽  
Daniel R. Hyduke ◽  
Andrew Williams ◽  
Roland Frötschl ◽  
...  
Keyword(s):  
High Throughput ◽  
Human Cancer ◽  
High Sensitivity ◽  
Chromosome Damage ◽  
Genetic Toxicology ◽  
Chemical Screening ◽  
Cell Assays ◽  
Development And Validation ◽  
Positive Results

Interpretation of positive genotoxicity findings using the current in vitro testing battery is a major challenge to industry and regulatory agencies. These tests, especially mammalian cell assays, have high sensitivity but suffer from low specificity, leading to high rates of irrelevant positive findings (i.e., positive results in vitro that are not relevant to human cancer hazard). We developed an in vitro transcriptomic biomarker-based approach that provides biological relevance to positive genotoxicity assay data, particularly for in vitro chromosome damage assays, and propose its application for assessing the relevance of the in vitro positive results to carcinogenic hazard. The transcriptomic biomarker TGx-DDI (previously known as TGx-28.65) readily distinguishes DNA damage-inducing (DDI) agents from non-DDI agents. In this study, we demonstrated the ability of the biomarker to classify 45 test agents across a broad set of chemical classes as DDI or non-DDI. Furthermore, we assessed the biomarker’s utility in derisking known irrelevant positive agents and evaluated its performance across analytical platforms. We correctly classified 90% (9 of 10) of chemicals with irrelevant positive findings in in vitro chromosome damage assays as negative. We developed a standardized experimental and analytical protocol for our transcriptomics biomarker, as well as an enhanced application of TGx-DDI for high-throughput cell-based genotoxicity testing using nCounter technology. This biomarker can be integrated in genetic hazard assessment as a follow-up to positive chromosome damage findings. In addition, we propose how it might be used in chemical screening and assessment. This approach offers an opportunity to significantly improve risk assessment and reduce cost.

New Imidazole Inhibitors of Mycobacterial FtsZ: the Way from High-Throughput Molecular Screening in Grid up to in vitro Verification

2016 ◽  
Vol 12 (3) ◽  
pp. 43-55 ◽  
Author(s):  
P.A. Karpov ◽  
◽  
O.M. Demchuk ◽  
V.M. Britsun ◽  
D.I. Lytvyn ◽  
...  
Keyword(s):  
High Throughput ◽  
Molecular Screening ◽  
The Way

A Functional High-Throughput Assay of Myelination in Vitro

2013 ◽  
Author(s):  
Michael J. Moore
Keyword(s):  
High Throughput ◽  
High Throughput Assay

In vitro Cytotoxicity and Genotoxicity Analysis of Ten Tannery Chemicals Using SOS/umu Tests and High-content In vitro Micronucleus Tests

2018 ◽  
Vol 21 (4) ◽  
pp. 262-270 ◽  
Author(s):  
Zehao Huang ◽  
Na Li ◽  
Kaifeng Rao ◽  
Cuiting Liu ◽  
Zijian Wang ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
A549 Cells ◽  
Quantitative Structure Activity Relationship ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Effects ◽  
Qsar Analysis ◽  
Cell Assays ◽  
Micronucleus Tests ◽  
Damaging Effects

Background: More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. Objective: This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. Materials and Methods: DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. Conclusion: The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals.

In Vitro High Throughput Phage Display Selection of Ovarian Cancer Avid Phage Clones for Near-Infrared Optical Imaging

2015 ◽  
Vol 17 (10) ◽  
pp. 859-867 ◽  
Author(s):  
Mette Soendergaard ◽  
Jessica Newton-Northup ◽  
Susan Deutscher
Keyword(s):  
Ovarian Cancer ◽  
Phage Display ◽  
Optical Imaging ◽  
High Throughput ◽  
Near Infrared ◽  
Selection Of
Sign in / Sign up

Export Citation Format

Share Document