Search results for "genetic instability"
showing 3 items of 3 documents
How to untie G-quadruplex knots and why?
2021
International audience; For over two decades, the prime objective of the chemical biology community studying G-quadruplexes (G4s) has been to use chemicals to interact with and stabilize G4s in cells to obtain mechanistic interpretations. This strategy has been undoubtedly successful, as demonstrated by recent advances. However, these insights have also led to a fundamental rethinking of G4-targeting strategies: due to the prevalence of G4s in the human genome, transcriptome, and ncRNAome (collectively referred to as the G4ome), and their involvement in human diseases, should we continue developing G4-stabilizing ligands or should we invest in designing molecular tools to unfold G4s? Here, …
In Vitro Assessment of the Genotoxic Hazard of Novel Hydroxamic Acid- and Benzamide-Type Histone Deacetylase Inhibitors (HDACi)
2020
Histone deacetylase inhibitors (HDACi) are already approved for the therapy of leukemias. Since they are also emerging candidate compounds for the treatment of non-malignant diseases, HDACi with a wide therapeutic window and low hazard potential are desirable. Here, we investigated a panel of 12 novel hydroxamic acid- and benzamide-type HDACi employing non-malignant V79 hamster cells as toxicology guideline-conform in vitro model. HDACi causing a &ge
Arsenite-induced aneuploidy following short and long-term exposure in mammalian cells
2009
We studied the long-term progression of chromosomal instability in V79 cells treated acutely with arsenite (10mM, 24 hr) followed by growth in arsenic-free medium for 120 cell generations. Indirect immunostaining using anti-ß-tubulin antibody showed severe alterations in spindle morphology after only 6 h treatment and cytogenetic investigations carried out at the end of treatment revealed that the percentage of cells with 21 chromosomes (modal number of the cell line) decreased, making way for aneuploid cells. The acquired instability remained and propagated within the cell population. Moreover, we treated V79-derived G12 cells with sub-lethal doses (0.1-1.0 μM) of arsenite for 10 days foll…