Abstract
<Purpose> Most cancers have been found to have numerical alterations of chromosomes, know as aneuploidy. However, very little is known about the oncogenic role of aneuploidy. We aimed to study what numerical alteration of chromosomes is in oncogenic transformation.
<Materials and Methods> we used tetraploid, triploid mouse cells from the primary cells derived from 13 days embryo of mouse without p53 gene functions. We examined micronuclei frequency as an index of chromosome nondisjunctions, and number of pH2AX-53BP1 foci as an index of DNA double strand breaks in triploid cells in comparison with tetraploid cells. We analyzed doubling time of cells for cell growth rate in triploid cells in comparison with tetraploid cells. We compared anchorage independent growth of triploid cells in 1.5% methylcellulose medium and tetraploid cells as an index of oncogenic transformation in vitro, and their ability to form tumors in vivo.
<Results> Tetraploid and triploid cells were cloned in p53 (-/-) mouse cells. Micronuclei frequency of triploid cells Micronuclei frequency of p53 (-/-) triploid cells show up to a 2-fold increase in tetraploid cells. On the other hand, Number of pH2AX-53BP1 foci was not changed in triploid and tetraploid cells. Cell growth rate of p53 (-/-) triploid cells was increased. Anchorage independent growth and tumorigenicity were found only in p53 (-/-) triploid cells.
<Conclution> In comparison to tetraploid cells, chromosome nondisjunctions occur significantly in triploid cells. Increased cell growth rate in triploid cells in comparison with tetraploid cells promotes the accumulations of the aberrations. Therefore, only triploid cells were transformed
