| Abstract: |
Recent studies have proposed that tumor necrosis factor α (TNF-α) and ionizing radiation induce apoptosis by activating hydrolysis of sphingomyelin to ceramide. Bcl-2 and a related gene, Bcl-X, inhibit several forms of apoptosis. Herein, we report that internucleosomal DNA fragmentation, characteristic of apoptosis and induced by ionizing radiation, is accompanied by concomitant decreases in Bcl-2 and Bcl-X mRNA levels in HL-60 and U-937 human leukemia cells. Apoptotic DNA fragmentation after exposure to TNF-α and C2-ceramide was also associated with down-regulation of Bcl-2 mRNA in HL-60 and U-937 cells, while Bcl-X mRNA production was unaffected. These results suggest that modulation of Bcl-2 gene expression may be a target for ceramide-mediated apoptosis following exposure to ionizing radiation and TNF-α. Changes in Bcl-2 expression may be the basis for the interactive killing observed between radiation and TNF-a in some human and tumor cells. © 1995, American Association for Cancer Research. All rights reserved. |
| Keywords: |
controlled study; leukemia; human cell; proto-oncogene proteins; radiation dose; combined modality therapy; cell death; dna damage; apoptosis; gene expression; down-regulation; tumor cells, cultured; gene expression regulation; molecular sequence data; tumor necrosis factor alpha; rna, messenger; gene repression; dna, neoplasm; ionizing radiation; base sequence; proto-oncogene proteins c-bcl-2; leukemia cell line; tumor necrosis factor; ceramide; ceramides; gene expression regulation, leukemic; dna fragment; messenger rna synthesis; human; priority journal; article; support, u.s. gov't, p.h.s.
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