[Effect of on various cell lines of p53 cDNA, expressed under the control of an exogenous homologous promotor].

Previous studies indicate that the wild-type p53 (unlike its mutant forms present in tumor cells) possesses growth suppressor activity specific for transformed cells. However, recombinant p53 gene governed by strong heterologous promoters was used in most of these experiments, that resulting in overexpression of p53. In order to create more physiologically adequate system, we placed the wild-type p53 gene and the His273 mutant under control of homologous p53 gene promoter within self- inactivating retroviral vector. Recombinant viral stocks were used to infect LIM1215, SW480, A431, 293, HeLa and K562 cell lines. These cell lines were found to be highly sensitive to the wild-type p53. The only cell line (LIM1215), that produced few viable colonies expressing wild-type p53, initially contained in its genome two unmodified alleles of the p53 gene. For the cell line HeLa initial proliferation of resistant colonies was observed, however, after a week, the cells stopped to divide and died due to apoptosis. Expression of the mutant (His273) p53 was tolerated by most cell lines, although in HeLa cells the doubling time and density of confluent culture were slightly reduced. These cells become more dependent on serum and factors from the culture medium, contrary ti the cell lines SW480 and A431 expressing His273 p53.