Genetic stability of senescence reverted cells: genome reduction division of polyploidy cells, aneuploidy and neoplasia.
Cell senescence from exhausted cell expansions to cells with short, dysfunctional telomeres is considered to be a non-replicative, irreversible state with possibility in tumor therapy. This leads to questions of senescence-stability which in genomic-probe, manipulated senescent flat cells resulted in reversions to mitotic cells. Additionally, rarer mitoses were present spontaneously in months, old, live flat cell cultures. These latter senescence-escaped cells were analyzed by cytogenetics to determine their origin from either stable G(0)/G(1) diploid and/or from unstable endopolyploid cells. Endo-polyploidization in senescence is associated with re-replication of genomically damaged G(2)/M cells. One source for genomic damage is senescence-specific occurrence of heterochromatization. It causes gluing of chromosomes together with consequent mal-segregations in mitosis which was a feature of the present reverted cells. In addition endo-polyploidy cycled with the characteristic presence of diplochromosomes (i.e., pairs of sister chromosomes) undergoing two consecutive bipolar divisions into genome reduced cells. Both diploid and tetraploid, aneuploid cells were also present as reverted cells. For in vitro cell senescence reversion to mitotic cells is therefore, concluded to be associated with occurrence of genomic instability. These results are discussed with reference to a meiotic-like somatic cell division of cycling endopolyploidy and as a possible mechanism of aneuploidization in tumor development. The extracellular matrix is evaluated in regard to a role as a protective shield against nuclear budding-offs (karyoplasts) from the flat cells to form mitotically-capable reverted cells.
Walen
Kirsten H
KH
Virus and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, California 94804, USA. kwalen@dhs.ca.gov
D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics*; D020090:Chromosome Segregation / Q000502:physiology; D003582:Cytogenetics; D005109:Extracellular Matrix / Q000378:metabolism; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D011003:Ploidies