Phosphatase Inhibitors and Premature Chromosome Condensation in Human Peripheral Lymphocytes at Different Cell-Cycle Phases

1999 ◽  
Vol 25 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Reiko Kanda ◽  
Kiyomi Eguchi-Kasai ◽  
Isamu Hayata
2005 ◽  
Vol 53 (3) ◽  
pp. 391-394 ◽  
Author(s):  
Malgorzata I. Srebniak ◽  
Gizela G. Trapp ◽  
Angelika K. Wawrzkiewicz ◽  
Wojciech Kaźmierczak ◽  
Andrzej K. Wiczkowski

An increased number of chromosome plates can be obtained by use of calyculin A (CLA). CLA is an inhibitor of protein phosphatases (type 1 and type 2A serine/threonine). Inactivation of these phosphatases leads to premature chromosome condensation (PCC) in all phases of the cell cycle; thus, it is possible to investigate both metaphase and G2-PCC chromosomes. Amniotic fluid (AF) cultures were treated with calyculin A (CLA). GTG banding was obtained. Using this method it is possible to investigate all cell cycle phases, GTG banding, chromosomal breaks, and rates of PCD on the same preparation. Analyses of AF cultures treated with CLA allow complex studies on fetal genetic material. This work presents potential usefulness of CLA for cytogenetic prenatal diagnosis.


Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1123 ◽  
Author(s):  
Pantelias ◽  
Karachristou ◽  
Georgakilas ◽  
Terzoudi

The discovery of chromothripsis in cancer genomes challenges the long-standing concept of carcinogenesis as the result of progressive genetic events. Despite recent advances in describing chromothripsis, its mechanistic origin remains elusive. The prevailing conception is that it arises from a massive accumulation of fragmented DNA inside micronuclei (MN), whose defective nuclear envelope ruptures or leads to aberrant DNA replication, before main nuclei enter mitosis. An alternative hypothesis is that the premature chromosome condensation (PCC) dynamics in asynchronous micronucleated cells underlie chromosome shattering in a single catastrophic event, a hallmark of chromothripsis. Specifically, when main nuclei enter mitosis, premature chromatin condensation provokes the shattering of chromosomes entrapped inside MN, if they are still undergoing DNA replication. To test this hypothesis, the agent RO-3306, a selective ATP-competitive inhibitor of CDK1 that promotes cell cycle arrest at the G2/M boundary, was used in this study to control the degree of cell cycle asynchrony between main nuclei and MN. By delaying the entrance of main nuclei into mitosis, additional time was allowed for the completion of DNA replication and duplication of chromosomes inside MN. We performed interphase cytogenetic analysis using asynchronous micronucleated cells generated by exposure of human lymphocytes to γ-rays, and heterophasic multinucleated Chinese hamster ovary (CHO) cells generated by cell fusion procedures. Our results demonstrate that the PCC dynamics during asynchronous mitosis in micronucleated or multinucleated cells are an important determinant of chromosome shattering and may underlie the mechanistic origin of chromothripsis.


1977 ◽  
Vol 91 (1) ◽  
pp. 131-141 ◽  
Author(s):  
Potu N. Rao ◽  
Barbara Wilson ◽  
Theodore T. Puck

2006 ◽  
Vol 6 ◽  
pp. 1174-1190 ◽  
Author(s):  
Vasiliki I. Hatzi ◽  
Georgia I. Terzoudi ◽  
Christina Paraskevopoulou ◽  
Vasilios Makropoulos ◽  
Demetrios P. Matthopoulos ◽  
...  

Nowadays, there is a constantly increasing concern regarding the mutagenic and carcinogenic potential of a variety of harmful environmental factors to which humans are exposed in their natural and anthropogenic environment. These factors exert their hazardous potential in humans' personal (diet, smoking, pharmaceuticals, cosmetics) and occupational environment that constitute part of the anthropogenic environment. It is well known that genetic damage due to these factors has dramatic implications for human health. Since most of the environmental genotoxic factors induce arrest or delay in cell cycle progression, the conventional analysis of chromosomes at metaphase may underestimate their genotoxic potential. Premature Chromosome Condensation (PCC) induced either by means of cell fusion or specific chemicals, enables the microscopic visualization of interphase chromosomes whose morphology depends on the cell cycle stage, as well as the analysis of structural and numerical aberrations at the G1 and G2 phases of the cell cycle. The PCC has been successfully used in problems involving cell cycle analysis, diagnosis and prognosis of human leukaemia, assessment of interphase chromosome malformations resulting from exposure to radiation or chemicals, as well as elucidation of the mechanisms underlying the conversion of DNA damage into chromosomal damage. In this report, particular emphasis is given to the advantages of the PCC methodology used as an alternative to conventional metaphase analysis in answering questions in the fields of radiobiology, biological dosimetry, toxicogenetics, clinical cytogenetics and experimental therapeutics.


Sign in / Sign up

Export Citation Format

Share Document