Related Experiment Videos
Chromatin compaction and tumor cell radiosensitivity at 2 gray
J D Chapman1, C C Stobbe, Y Matsumoto
1Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
American Journal of Clinical Oncology
|October 5, 2001
Summary
Compacted chromatin in human tumor cells correlates with radiosensitivity. This finding may lead to a new assay for predicting radiation response and identifying drugs that enhance cancer treatment effectiveness.
Area of Science:
- Cell Biology
- Radiation Oncology
- Cancer Research
Background:
- Mammalian cells, including lymphocytes and radiation-hypersensitive mutants, exhibit chromatin compaction.
- Compacted chromatin is associated with hypersensitivity to ionizing radiation via single-hit inactivation kinetics (alpha).
Purpose of the Study:
- To investigate if interphase compacted chromatin is the target determining variable radiosensitivity (alpha-parameters and SF2Gy) in human tumor cell lines.
- To explore the potential of chromatin compaction analysis as a predictive assay for tumor radiosensitivity.
Main Methods:
- Quantitative analysis of electron microscope images of interphase nuclei from six human tumor cell lines with varying radiosensitivity.
- Digitization and optical scanning of pixel densities to determine the percentage of compacted chromatin.
- Correlation analysis between compacted chromatin percentage and alpha-inactivation parameters.
Main Results:
- A significant positive correlation was found between the percentage of nuclear pixels representing compacted chromatin and the alpha-inactivation parameters.
- Radiosensitivity of human tumor cell lines, specifically their alpha-parameters, is strongly associated with the degree of chromatin compaction in interphase.
Conclusions:
- Interphase compacted chromatin is a key target influencing intrinsic tumor radiosensitivity.
- Digital analysis of chromatin compaction in biopsy specimens could serve as a rapid assay for predicting radiosensitivity.
- Inhibitors of protein (histone) phosphatases that induce chromatin compaction can radiosensitize cells, offering potential therapeutic strategies.