[Apoptotic cell death in rat embryo fibroblasts transformed by EiA + cHa-RAS oncogenes after gamma irradiation].
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.
Bulavin
D V
DV
Institute of Cytology, Russian Academy of Sciences, St. Petersburg.
Tararova
N D
ND
Aksenov
N D
ND
Pospelov
V A
VA
Pospelova
T V
TV
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002453:Cell Cycle / Q000528:radiation effects; D002461:Cell Line, Transformed; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects*; D005720:Gamma Rays; D011905:Genes, ras; D009857:Oncogenes; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology; D016283:Proto-Oncogene Proteins p21(ras) / Q000276:immunology; D051381:Rats
D017500:Adenovirus E1A Proteins; D018809:Proliferating Cell Nuclear Antigen; D016283:Proto-Oncogene Proteins p21(ras)