DNA-DAMAGE CAN INDUCE APOPTOSIS IN PROLIFERATING LYMPHOID-CELLS VIA P53-INDEPENDENT MECHANISMS INHIBITABLE BY BCL-2
Details
Publication Year 1994-10-21,Volume 79,Issue #2,Page 329-339
Journal Title
CELL
Publication Type
Journal Article
Abstract
The roles of p53 as an inducer and Bcl-2 as an inhibitor of apoptotic death were explored in lymphoid cells. Lymphocytes from p53(-/-) mice were radioresistant, but unexpectedly, cycling T lymphoma cells and mitogenically activated T lymphocytes from these animals underwent apoptosis after irradiation or genotoxic drug treatment. Hence, p53 is not the only mediator of apoptosis provoked by DNA damage. Irradiated p53(-/-) lymphoblasts expressing Bcl-2 were subject to growth arrest but resisted apoptosis. Their accumulation in G1 as well as G2 is suggestive of a p53-independent DNA-damage G1 checkpoint. Since Bcl-2 increased the clonogenic survival of the irradiated cells, expression of survival genes may pose a greater impediment to genotoxic cancer therapy than loss of p53.
Publisher
CELL PRESS
Keywords
WILD-TYPE P53; MYELOID-LEUKEMIA CELLS; DEATH GENE CED-3; CYCLE CONTROL; ERYTHROLEUKEMIA-CELLS; MICE DEFICIENT; STRAND BREAKS; MUTANT P53; PRE-B; PROTEIN
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Creation Date: 1994-10-21 12:00:00
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