Effect of Cystine Depletion on Growth-Arrested Human Diploid Fibroblasts

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Abstract
Preconfluent and growing human diploid fibroblasts started to die within a day in cystine-free medium. When cell growth was arrested by allowing cells to approach confluency, by the removal of serum, or by the addition of inhibitors of protein or RNA synthesis, cells could survive cystine depletion. However, when cell growth was arrested by the addition of DNA synthesis inhibitors, the cells could not survive cystine depletion. The rate of decrease in the cellular glutathione content after cystine depletion was slower under conditions where cells survived than under those where cells died. Under conditions where cells survived, a considerable amount of glutathione was retained in the cells even after two days of cystine depletion. These observations are consistent with an important role for glutathione in the survival of the human fibroblasts.