Cells synchronized by the mitotic selection technique were treated with hypertonic medium (525-584 mosm from myo-inositol, glucose, sorbitol, KCl, or NaCl) and X-irradiated either in mitosis, G1, or S phase. The hypertonic treatments did not reduce the plating efficiency of the un-irradiated cells, but they did produce radiosensitization (more cell killing and chromosomal aberrations), which increased as the synchronous cells were treated and irradiated in more resistant phases of the cell cycle. For example, treatment of sensitive mitotic cells produced no radiosensitization, whereas, treatment of resistant S phase cells, either before or after irradiation, resulted in radiosensitization characterized by dose modifying factors of 1.20 or 1.45 for treatments at 20 or 37°C, respectively. Radiosensitization was associated with condensation of chromatin observed by electron microscopy. At 20°C, the effect of hypertonic treatment was attributed equally to increase in lethal damage and to inhibition of repair at 20°C of potentially lethal damage. Furthermore, a relatively long period of 10-20 min was required both for the effect to occur and to disappear once the treatment was terminated. At 37°C, however, the radiosensitizing effect persisted for less than 1 min once the treatment was terminated and was due to an increase in the rapid (T1/2 of 1-2 min) fixation of potentially lethal damage. It was postulated that single lesions in chromatin fibers which were packed together within 30 sec after hypertonic treatment interacted to produce potentially lethal lesions. These potentially lethal lesions were then either confirmed at 37°C into lethal lesions or were rapidly converted back into single sublethal lesions when the chromatin was dispersed within 30 sec after transfer of the cells back into isotonic medium.

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