Cell transformation by simian virus 40 mutants.
The role played by the early region of simian virus 40 (SV40) in cellular transformation has been investigated using a series of constructed double mutants which associated a d1-54-59 mutation with either a tsA mutation or a deletion located in the 3'-terminal part of the A gene. The ability of secondary mouse or rat embryo infected cells to clone at low cell density was used to select transformants, which were later tested for anchorage-independent growth. The results show that the conversion of a mouse or rat embryo cell into a continuous cell line requires the permanent expression of the A gene. SV40 mutants were also used in conjunction with tumor promoters to induce anchorage-independent growth of Swiss 3T3 cells. SV40-tsA-infected cells produced macrocolonies when plated in soft-agar at the restrictive temperature of 39 degrees C in the presence of the potent tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). At the permissive temperature of 33 degrees C, TPA increased the number of soft-agar clones about 4-fold. A good correlation between the formation of macrocolonies at 39 degrees C and the reported promoting activity of various compounds, including teleocidin B and anthralin, was observed. Saccharin behaved in this system as a weak promoter, since an effect is observed at concentrations around 1 X 10(-4) M, while the effect of TPA is clearly detected at 1.6 X 10(-10) M. The results suggest that SV40-tsA-infected Swiss 3T3 cells might provide a quick and easy test for tumor promoters.
D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication; D004622:Embryo, Mammalian; D005814:Genes, Viral; D051379:Mice; D009154:Mutation; D051381:Rats; D013539:Simian virus 40 / Q000187:drug effects / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014779:Virus Replication
D013755:Tetradecanoylphorbol Acetate