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Stobbe CC, Park SJ, Chapman JD
The radiation hypersensitivity of cells at mitosis
International Journal of Radiation Biology (2002) 78:1149-1157.
Abstract
Purpose: Mitotic cells are hypersensitive to ionizing radiation, exhibiting single-hit inactivation coefficients near to those of repair deficient cell lines and lymphocytes. To elucidate possible mechanisms for this hypersensitivity, the kinetics of oxygen radiosensitization, the proportion of indirect effect by OH radicals and the kinetics of radiation- induced DNA strand breakage in the chromatin of mitotic cells were investigated. Materials and methods: Synchronized populations kof >90% mitotic HT-29 cells were obtained by the mitotic shake-off method. Cells were irradiated at less than or equal to4degreesC with Cs-137 gamma-rays. Cellular oxygen concentration was varied by gassing cell suspensions prior to and during irradiation with mixtures of pure N-2 that contained 5% CO2 and measured quantities of O-2. The indirect effect of OH radicals was investigated with the radical scavenger, DMSO. DNA strand breakage was measured by the comet assay. Results: Mitotic HT-29 cell inactivation is well described by a single- hit inactivation coefficient (alpha) of 1/14 +/- 0.06 Gy(-1). The oxygen enhancement ratio of mitotic cells (at 10% survival) was found to be similar to2.0, significantly lower than the value of 2.8 measured for interphase (asynchronous) cells. More than 60% of mitotica cell killing was eliminated when the media contained 2 M DMSO, indicating that indirect effect is as important in the killing of mitotic cells as it is for interphase cells. The chromatin in mitotica cells was found to be similar to2.8 times more sensitive to radiation-induced DNA single-strand breakage than the chromatin of interphase cells. Conclusions: The alpha-inactivation coefficient of mitotic HT- 29 cells was similar to30 times larger than that of interphase cells. Mitotic cell chromatin appears to contain to contain intrinsic DNA breaks that are not lethal. In addition, chromatin in mitotic cells was found to be more susceptible to radiation-induced DNA strand-breakage than the dispersed chromatin of interphase cells. How the enhanced production of these simple DNA lesions that are usually reparable) translates into the lethal (non-reparable) events associated with alpha- inactivation is not known. The compaction/dispersion status of DNA throughout the cell cycle appears to be an important factor for determining intrinsic cell radiosensitivity and might be manipulated for radiotherapeutic advantage.
Note
Publication Date: 2002-12-01.
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