Related Experiment Videos
Modifiers of radiation-induced apoptosis
R E Langley1, S T Palayoor, C N Coleman
1Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts.
Radiation Research
|December 1, 1993
Summary
Ionizing radiation induces apoptosis-like cell death in cancer cells. Different agents can trigger this DNA fragmentation, suggesting distinct modification pathways for radiation-induced apoptosis versus classical cell killing.
Area of Science:
- Molecular Biology
- Cell Death Mechanisms
- Radiation Biology
Background:
- Ionizing radiation can induce apoptosis-like cell death in EL4 murine lymphoma and F9 murine teratocarcinoma cells.
- Apoptosis, characterized by internucleosomal DNA fragmentation, differs from classical clonogenic cell killing by radiation.
Purpose of the Study:
- To investigate whether the mechanism of radiation-induced apoptosis differs from classical clonogenic cell killing.
- To determine if these two endpoints of radiation action can be differentially modulated.
Main Methods:
- Treatment of EL4 and F9 cells with various agents, including tert-butyl hydroperoxide, diazenedicarboxylic acid bis(N,N-piperidide), and etoposide.
- Assessment of internucleosomal DNA fragmentation as a marker of apoptosis.
- Evaluation of the inhibitory effects of 3-aminobenzamide, dibutryl cyclic AMP, and 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl on radiation-induced DNA fragmentation.
Main Results:
- Diverse agents induced internucleosomal DNA fragmentation, characteristic of apoptosis, in both cell lines.
- Hydrogen peroxide did not induce significant DNA fragmentation at radiation-equivalent concentrations.
- Radiation-induced DNA fragmentation was inhibited by 3-aminobenzamide, dibutryl cyclic AMP, and 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, with cell-line-specific variations.
Conclusions:
- The mechanism of apoptosis induction by radiation may differ from classical clonogenic cell killing.
- These distinct mechanisms suggest potential for differential modulation of radiation's effects on cell death pathways.
- Cell-specific differences exist in the modulation of radiation-induced DNA fragmentation.