DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by Bcl-2.

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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.

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关键词：

Animals Mice, Inbred C57BL Mice Tumor Cells, Cultured Lymphoma, T-Cell Dexamethasone Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Apoptosis Mice, Transgenic