Genetic analysis of control of proliferation in fibroblastic cells in culture. II. Alteration in proliferative and survival phenotypes in a set of temperature-sensitive mutants of rat 3Y1 cells after infection or transformation with simian virus 40.

Mutants of rat 3Y1 fibroblasts, temperature sensitive for proliferation or survival and which represent each of eight complementation groups, were examined to determine whether cells made quiescent at confluence at 33.8 degrees C (permissive temperature) can be stimulated to enter S phase at 39.8 degrees C (nonpermissive temperature) by 20% serum or by infection with simian virus 40 (SV40). Three mutants with a short survival at 39.8 degrees C did not enter S phase at 39.8 degrees C under either condition. The remaining five entered S at 39.8 degrees C by infection with SV40. However, only one of these five entered S in response to high serum. After transformation with SV40, three mutants accumulating at 39.8 degrees C with a predominantly 2n (G1) DNA content did not proliferate, there was a rapid and extensive cell death, and the cells had a DNA content similar to that seen in randomly proliferating populations. The other two mutants, accumulating at 39.8 degrees C with a predominantly 2n or 2n X 4n DNA content, proliferated at this temperature after transformation with SV40. These results clearly indicate that SV40 interacts closely with cellular ts lesions related to control of proliferation and cell survival.