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| Loss of ceramide production confers resistance to radiation-induced apoptosis |
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| Author(s): Chmura SJ, Nodzenski E, Beckett MA, Kufe DW, Quintans J, Weichselbaum RR |
| Source: CANCER RESEARCH Volume: 57 Issue: 7 Pages: 1270-1275 Published: APR 1 1997 |
| Times Cited: 115 References: 28 |
| Abstract: Ionizing radiation mediates cell death, in part, through chromosomal damage following one or more cell divisions, X-rays also induce programmed cell death (apoptosis) in some cell types both in vitro and in vivo, Both neutral and acidic sphingomyelinases, which generate the lipid second messenger ceramide, are reported to induce apoptosis following ionizing radiation and other death signals such as tumor necrosis factor Lu and Fas ligand, Herein we report that a loss of ceramide production from a neutral sphingomyelinase generates a radioresistant phenotype as measured by a marked decrease in apoptosis, A WEHI-231 subline made deficient in ceramide production was found to be resistant to apoptosis compared with the parental subline following treatment with X-rays, The resistant subline underwent two to three subsequent cell divisions following X-irradiation, confirming that X-rays induce cell death through both mitotic and apoptotic mechanisms, These data suggest that loss of ceramide production following X-rays represents an extranuclear mechanism for the development of radioresistance, Modulation of extranuclear signals may increase tumor cell killing following radiation and represent new cellular targets for cancer therapy. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CHICAGO, DEPT PATHOL, CHICAGO, IL 60637 USA
2. UNIV CHICAGO, DEPT RADIAT & CELLULAR ONCOL, DIV BIOL SCI, CHICAGO, IL 60637 USA
3. UNIV CHICAGO, PRITZKER SCH MED, CHICAGO, IL 60637 USA
4. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, PHARMACOL LAB, BOSTON, MA 02115 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: WQ625 |
| ISSN: 0008-5472 |
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