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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Finally, there is some evidence that ATR may have a role in regulating the spindle apparatus to which the centromeres are attached and then pulled apart into new cells during cell division. It is thought that ATR may facilitate attachment of the centromeres to the spindle, which means that ATR inhibition could lead to whole chromosome mis-segregation, suggesting that ATR inhibitors may be particularly effective in cancers with a high level of RS and chromosomal instability.
Problems on Excess of Inorganic Chemical Compounds for Mankind
Published in Jul Låg, Geomedicine, 2017
Jan Alexander, Jetmund Ringstad, Jan Aaseth
Of considerable concern are metal compounds causing cancer. Development of cancer is an incompletely understood and complicated multistage process. Metals could, in principle, influence this process at several stages. It is well known that some metal compounds cause genetic damage, affecting DNA repair as well as the spindle apparatus during cell division.32
The human oocyte: Controlled-rate cooling Controlled-rate cooling
Published in David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham, Textbook of Assisted Reproductive Techniques, 2017
Another structure that can be damaged by cryopreservation is the meiotic spindle, which is composed of microtubules and is important for chromosome segregation. At the time of fertilization, upturn of meiosis takes place, separating the chromatids attached to the meiotic spindle, expelling one set into the second polar body and the other into the female pronucleus (44). The meiotic spindle apparatus is a dynamic structure and it has been demonstrated to depolymerize when exposed to low temperatures (45). Nevertheless, after a return to normal conditions, the spindle is able to significantly reassemble (21, 46, 47). This structure must work correctly to achieve accurate chromosome segregation; subsequent impaired repolymerization at warming may lead to misaggregation of chromatids and aneuploidy (48).
Genotoxic and mutagenic studies of teratogens in developing rat and mouse
Published in Drug and Chemical Toxicology, 2019
Eyyüp Rencüzoğulları, Muhsin Aydın
Micronucleus is a small nucleus that forms whenever a chromosome or a fragment of a chromosome is not incorporated into one of the daughter nuclei during the cell division. It is found outside the main nucleus and formed in telophase due to the acentric chromosomal or chromatid fractures. Also, it could be formed during the telophase from one or a few chromosomes or chromatids that lag behind the anaphase (anaphase bridge) (Surrallés et al. 1995). In addition, multipolar anaphase and telophase could cause MN formation (Topaktas and Rencuzogullari 2010). Chromosome loss or nondisjunction of chromosomes that may lead to MN formation is one of the important events that is observed in cancer and aging. This is probably the result of disruption in spindle apparatus and centromere or condensation of the chromosome prior to metaphase (Dellarco et al. 1985). Thus, both the clastogenic and the aneugenic effects can be determined by the MN test (Kirsch-Volders et al. 1997, Norppa and Falck 2003). In previous studies, the increase in MN frequency in peripheral blood lymphocytes from cancer patients was found to be as much as the MN frequency in the targeted cancer tissue (Cheng et al. 1996, Duffaud et al. 1997, Bonassi et al. 2007). In addition, in the study of Fenech et al. (1999), which have been conducted with an international collaboration, has clearly shown the relationship between MN and cancer in humans.
Assessment of the in vitro genotoxicity of TiO2 nanoparticles in a regulatory context
Published in Nanotoxicology, 2018
Sandrine Charles, Stéphane Jomini, Valérie Fessard, Emilie Bigorgne-Vizade, Christophe Rousselle, Cécile Michel
DNA damage can also arise through indirect mechanisms where the NPs do not physically interact with the DNA molecule, but with other cellular proteins such as those involved in cell division, DNA replication, transcription, and repair. Indeed, many of the proteins involved in the repair machinery possess metallic linked functions that may be disturbed by the NPs due to competition for biological sites or due to redox potential modification (Carriere et al. 2017). This hypothesis was highlighted in a microarray test using plasmid containing fluorescent nucleotides showing decreased nucleotide excision repair (NER) and base excision repair (BER) activities in A549 cells exposed to TiO2-NPs (Jugan et al. 2012) and confirmed in a direct in vitro test on the same cell line (Armand et al. 2016). TiO2-NPs have a very high affinity for phosphate groups, possibly engendering a high reactivity and trapping against DNA itself (DNA contains high levels of phosphate residues) and phosphorylation–dephosphorylation reactions, such as those implicated in DNA repair machinery (Carriere et al. 2017). Finally, another mode of action proposed for TiO2-NPs is an alteration of the mitotic spindle apparatus. Some publications reported disturbance of mitosis, and abnormal multipolar spindle formation, chromosomal alignment, and segregation during anaphase and telophase, as well as disturbance of the cell cycle checkpoint function (Magdolenova et al. 2014).
Global methylation profiles in buccal cells of long-term smokers and moist snuff consumers
Published in Biomarkers, 2018
Walter J. Jessen, Michael F. Borgerding, G. L. Prasad
All five MSR network analyses-identified processes are involved in cell cycle regulation (60 total genes, 5% (3) are hyper- or hypo-methylated). A prominent feature of this category is mitosis. The gene encoding cytoplasmic linker associated protein 2 (CLASP2), which promotes the stabilization of dynamic microtubules and fibronectin type III and SPRY domain containing 1 (FSD1), which associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis – were hypo-methylated and predicted to be down-regulated. A third mitosis gene, kinesin family member 15 (KIF15), maintains bipolar microtubule spindle apparatus in dividing cells and was methylated and predicted to be down-regulated.