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 microgram/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 microM mevastatin, an agent which is known to be capable to deactivate the ras function, cell viability decreased and apoptotic cells became abundant (approximately 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.