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Cell Biology International (2007) 31, 1447–1455 (Printed in Great Britain)

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Origin of diplochromosomal polyploidy in near-senescent fibroblast cultures: Heterochromatin, telomeres and chromosomal instability (CIN)

Kirsten H. Walen^ab*

^aViral and Rickettsial Disease Laboratory, California Department of Health Services, 850 Marina Bay Parkway, Richmond, CA 94804, USA
^bCROMOS, 763 Ocean Avenue, Richmond, CA 94801, USA

Abstract

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.

Key words: Epigenetics, Checkpoint controls, Re-replication, G2/M cells, Mitosis, Endopolyploidy.

^*Correspondence address: VRDL, California Department of Health Services, 850 Marina Bay Parkway, Richmond, CA 94804, USA. Tel.: +1 510 234 3375; fax: +1 510 234 3127.

Received 13 February 2007/24 April 2007; accepted 27 June 2007