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  • Title: [Apoptotic cell death in rat embryo fibroblasts transformed by EiA + cHa-RAS oncogenes after gamma irradiation].
    Author: Bulavin DV, Tararova ND, Aksenov ND, Pospelov VA, Pospelova TV.
    Journal: Tsitologiia; 1998; 40(12):1017-24. PubMed ID: 10188216.
    Abstract:
    A mechanism of apoptotic death of normal rat embryo fibroblasts and of those transformed by E1A + cHa-Ras oncogenes following gamma irradiation has been investigated. The E1A + cHa-Ras transformed cells were shown to express wild type p53 which was able to trans-activate a reporter pG13-luc Plasmid. As a result of trans-activation, an accumulation of universal inhibitor of cyclin-dependent kinases--p21/Waf1 protein and an increase in the proportion of p21/Waf1 expressing cells were observed, The accumulated p21/Waf1 was found to bind with PCNA. The association with PCNA, however, did not lead to suppression of DNA replication according to the data of iododeoxyuridine (IdUr) incorporation. A high proportion of S-phase cells, in combination with cell cycle blocking in G2-phase, promoted polyploidization of E1A + cHa-Ras transformed cells after gamma irradiation. The polyploidic cells with DNA content equal and higher than 8c die 48-72 h following irradiation due to apoptosis. A significant proportion of E1A + cHa-Ras cells with incorporated IdUr contains labeled micronuclei, the fact being a morphological evidence of apoptosis of cells in S-phase of the cell cycle.
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