Chinese hamster Don cells, synchronized by removing metaphase cells from an asynchronous population, were x-irradiated or fixed in different parts of the cell cycle. Radiosensitivity, as measured by chromosomal aberrations, decreased by a factor of 2.6 as the cells moved from mitosis into S phase. This decrease in radiosensitivity correlated well with the dispersion of chromatin, which was visualized and quantitated by electron microscopy. The chromatin consisted of 70-Å fibers, each of which contained two 28-Å fibrils, and the distance, D, between the 70-Å fibers increased from an average value of 142 Å in mitotic cells with condensed chromatin to 196 Å in S phase cells with dispersed chromatin. The value of$1/D^{3}$ decreased, as for the frequency of aberrations, by a factor of 2.6 as the cells moved from mitosis into S phase. Based on (1) this correlation, (2) an increase in radiosensitivity associated with condensation of chromatin caused by hypertonic treatment and (3) other observations including the similarity in kinetics for repair of sublethal and potentially lethal lesions, a model was proposed to account for much of the variation in radiosensitivity during the cell cycle. In this model, potentially lethal and lethal lesions result from the interaction of single lesions in the 70-Å chromatin fibers. Interacting lesions may be produced in close proximity to one another by a single dose of radiation, or they may result from single sublethal lesions from one dose interacting with other single sublethal lesions produced by a second dose. Thus, the mitotic cells should be the most radiosensitive cells because their tightly packed chromatin fibers should provide the highest probability for interactions between lesions. However, the increase in radiosensitivity at the G1/ S border must be attributed to other mechanisms.

This content is only available as a PDF.