Equilibrium Between Cell Division and Apoptosis in Immortal Cells as an Alternative to the G1 Restriction Mechanism in Mammalian Cells

Abstract

Starvation arrests cultured mammalian cells in the G1 restriction point of the cell cycle, whereas cancer cells generally lose the regulatory control of the cell cycle. Human lymphocytes, infected with Epstein-Barr virus (EBV), also lose their cell cycle control and produce immortal lymphoblastoid cell lines. We show that during starvation, EBV-lymphoblasts override the cell cycle arrest in the G1 restriction point and continue cell division. Simultaneously, starvation activates apoptosis in an approximately half of the daughter cells in each cell generation. Continuos cell division and partial removal of cells by apoptosis results in stabilization of viable cell numbers, where a majority of viable cells are in the G1 phase of the cell cycle. In contrast to starvation, anticancer drug etoposide activates apoptosis indiscriminately in all EBV-lymphoblasts and convertes all the viable cells into apoptotic. We conclude that the removal of surplus cells by apoptosis may represent a survival mechanism of transformed (i.e. cancer) cell population in nutrient restricted conditions, whereas non-transformed mammalian cells are arrested in the G1 restriction point of the cell cycle.