Differential cell death in immortalized and non-immortalized cells at confluency.

Rat embryo fibroblast cells that have been immortalized by viral transfection have an altered cell cycle control. These cells have been observed to die via an apoptotic death when grown to confluency which, in at least one of the cell line pairs studied, was independent of the presence of wildtype or mutant p53. This confluency-dependent apoptotic cell death was observed in thirteen of fourteen rodent and human cell lines tested. In contrast, primary rodent and human cell strains (fibroblasts) entered a quiescent G1/G0 state at confluency. Two weeks later, these non-immortalized cells underwent necrosis, not apoptosis. As the medium was not replenished during this two week period, cell necrosis was probably due to deprivation of nutrients and growth factors. These results indicate that mechanisms of cell death may differ between transformed and non-transformed cells under physiological stressed situations, such as high cell density. It may be possible to exploit these differences to increase the efficacy of chemotherapeutic compounds towards neoplastic cells.