Origin of diplochromosomal polyploidy in near-senescent fibroblast cultures: heterochromatin, telomeres and chromosomal instability (CIN).
The near-senescence associated phenomena of increases in cells with chromosomal damage (CIN) and in endopolyploid mitotic cells were analyzed for possible inter-relationships by cytogenetics. Gross chromosomal abnormalities in all phases of mitosis were analyzed in situ. Hetrochromatization of telomeres, centromeres and interstitial chromatin regions (i.e., chromocenters/SAHF) were shown to be specific occurrences in the near-senescent phase. Stickiness between such chromatin regions caused breakage/fragmentation by anaphase-pulls on clumped chromosomes. Gluey heterochromatin is therefore, seen as a cause of CIN in near-senescence. Detrimental effects on chromosomes from heterochromatin have been observed for decades, and can be explained from chromatin remodeling in epigenetics. A consequence of genomic damage was re-replication to polyploidy of arrest-escaped cells with G2/M-DNA content. This second synthetic period produced diplochromosomal cells that cycled by bi-polar division into genome reduced cells. This sequence from h-chromatization to CIN and further to cycling endopolyploidy is believed to be a basic mechanism for the production of genetic variability in neoplasia.
Walen
Kirsten H
KH
Viral and Rickettsial Disease Laboratory, California Department of Health Services, 850 Marina Bay Parkway, Richmond, CA 94804, USA. kwalen@dhs.ca.gov
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line / Q000378:metabolism / Q000648:ultrastructure; D016922:Cellular Senescence / Q000235:genetics*; D002503:Centromere / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D043171:Chromosomal Instability / Q000235:genetics*; D020090:Chromosome Segregation; D002877:Chromosomes, Human / Q000235:genetics / Q000648:ultrastructure; D004171:Diploidy; D005260:Female; D005347:Fibroblasts / Q000502:physiology / Q000648:ultrastructure*; D006570:Heterochromatin / Q000235:genetics / Q000648:ultrastructure*; D006801:Humans; D011123:Polyploidy; D016615:Telomere / Q000235:genetics / Q000648:ultrastructure*; D014178:Translocation, Genetic / Q000235:genetics
D014408:Biomarkers, Tumor; D006570:Heterochromatin