Serum contains exogenous survival factors for fibroblasts. Removal of these exogenous factors causes inactivation of endogenous survival factors, subsequent release of a constitutively expressed apoptosis machinery from negative control and apoptosis. Inactivation of endogenous survival factors after serum withdrawal is mediated by reactive oxygen species and can be rapidly reversed through re-addition of serum. Oxidative inactivation of endogenous survival factors after depletion of exogenous survival factors as well as the process of reversion to the active state do not require protein synthesis, indicating the existence of a constitutively expressed regulatory system that controls the interaction of exogenous and endogenous survival factors.

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