Current Biology
Volume 5, Issue 4, April 1995, Pages 423-431
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Research Paper
Elevated levels of wild-type p53 induced by radiolabeling of cells leads to apoptosis or sustained growth arrest

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Abstract

Background: The tumor suppressor protein p53 regulates progression through the checkpoint between the G1 and S phases of the cell cycle in response to radiationor drug-induced DNA damage. We have examined potential p53-mediated effects of metabolically labeling cultured mammalian cells with [35S]methionine and [3H]thymidine, methods that are commonly used to study the biochemical properties, synthesis, processing and degradation of proteins and the replication of DNA in proliferating cells.

Results Wild-type p53 protein concentrations rapidly increased to high levels following metabolic radiolabeling of cells, as determined by four distinct assays. The increased concentration of wild-type p53 resulted in apoptosis of normal human peripheral blood lymphocytes and of murine T-cell acute lymphoblastic leukemia cells. In leukemia cells containing no p53, or only mutant p53 alleles, p53 protein levels were not increased and the cells did not undergo apoptosis in response to radioactive labeling. Radiolabeling of human diploid fibroblasts resulted in a prolonged growth arrest that was maintained for nearly three weeks.

Conclusion The results of experiments employing radiolabeling techniques to characterize various aspects of cellular physiology may be seriously influenced by the induction of aberrant cell-cycle arrest and/or apoptosis mediated by wild-type p53. Furthermore, our observations suggest that stabilization of wild-type p53 in response to irradiation may not act primarily to facilitate the repair of DNA damage by inducing a transient G1-phase arrest, but rather to ensure genetic stability through sustained cell-cycle arrest or apoptotic death of the damaged cells.

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Jo Yeargin and Martin Haas (corresponding author), Department of Biology and Cancer Center, University of California, San Diego, La Jolla, California 92093-0063, USA.