Antiapoptotic effect of ras in the apoptosis induced by serum deprivation and exposure to actinomycin D

Serum deprivation or exposure of NIH 3T3 cells to actinomycin D (0.25–1.0 mg/ml ; 1 h) was associated with the accumulation of numerous apoptotic cells, as identified by their condensed nuclei and the decrease in cell size. In contrasts, v-H-ras-transformed NIH 3T3 cells were found to be resistant to this apoptosis induction. When v-H-ras-transformed cells were first pretreated for 24 h with 50 μM mevastatin, an agent which is known to be capable to deactivate the ras funcion, cell viability decreased and apoptotic cells became abundant (~60–80%) 72 h after serum deprivation or exposure to actinomycin D. During the serum deprivation of NIH 3T3 cells, appearance of the apoptotic cells was preceded by G₁ phase arrest. Accumulation of cells in the G₁ phase was also observed in v-H-ras-transformed cells 24 h after serum deprivation. At later times (48–72 h), v-H-ras-transformed cells seemed to be capable of breaking through the G₁ arrest and were then found to be distributed normally in the cell cycle. Received: 6 May 1996 / Accepted: 2 September 1996