DNA-DAMAGE CAN INDUCE APOPTOSIS IN PROLIFERATING LYMPHOID-CELLS VIA P53-INDEPENDENT MECHANISMS INHIBITABLE BY BCL-2

被引：675

作者：

STRASSER, A ^{[1
]}

HARRIS, AW ^{[1
]}

JACKS, T ^{[1
]}

CORY, S ^{[1
]}

机构：

[1] MIT,HOWARD HUGHES MED INST,CTR CANC RES,CAMBRIDGE,MA 02139

来源：

CELL | 1994年 / 79卷 / 02期

关键词：

D O I：

10.1016/0092-8674(94)90201-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：329 / 339

页数：11

共 71 条

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