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The recovery from radiation-induced mitotic delay in asynchronous sarcoma-180 (S-180) ascites tumor cells has been analyzed in a manner analogous to the repair of sublethal damage. 200-R increments were separated by various fraction intervals (not exceeding the time necessary for mitosis to return to control levels) for total exposures up to 1600 R. The accumulated mitotic delay after the last exposure increment, in percent of an equivalent single exposure, decreased exponentially with overall treatment time in a bimodal fashion. An initial repair process displayed a half time of 2.3 h of overall elapsed time and was followed by a slower process with a half time of 15.1 h. Such a bimodal recovery provides an explanation of why fractionation intervals long with respect to the amitotic period resulting from a single 200 R exposure enhance mitotic delay over that of equivalent single exposures, while shorter fractionation intervals diminish it. It also predicts that mitotic delay vs. dose curves should bend toward the abscissa as the exposure time is increased with large single exposures and large fractionated exposures given over short fraction intervals.

Mouse ascites tumor cells were irradiated in vivo and the delay in cell division determined by periodic examination of mitotic index. Fractional exposures of 200 R were given eight times for a total of 1600 R. The effect on survival was determined 9 days after an inoculation of 4000 cells which had been removed from the irradiated animal. Survival was determined by counting the cells and was expressed as percentage of controls. It was found that fraction intervals of 0.5 and of 1 hour gave minimal delay and maximal survival. As the fractional interval was increased to 3 and to 4.8 hours, the delay became directly proportional to total radiation exposure and there was little recovery from lethal action as compared to the effect of other methods of exposure. It appeared that fractionation at 4.8-hour intervals tended to partially synchronize cells into later stages of the generation cycle; increased mitotic delay; and reduced survival as compared with effects of shorter fraction intervals.

Chinese hamster ovary fibroblasts (MI > 90%) were synchronized by mitotic selection and x-irradiated at two-hour intervals during the cell cycle with 150, 300, or 600 rad. Cell progression was monitored by pulse labeling with [3 H] TdR at one-hour intervals, followed by autoradiography and liquid scintillation counting. Irradiated mitotic and G1 cells were delayed in initiating DNA synthesis (0.4-2.7 hr), but the rate of entry into and out of S, the duration of S, and the rate of DNA synthesis remained unchanged. Cells irradiated during S incorporated [3 H] TdR at a reduced rate and were delayed in entering G2. The fraction of cells capable of entering S was not reduced by any time-dose combination. The delay in entering and leaving the S phase which resulted from a dose of 150 or 600 rad was about 40% of that from 300 rad. The division delay, however, increased linearly with dose and exponentially with cell age. The ratio of division delay to S delay for G1 cells irradiated with 150 and 300 rad was appro...

Sarcoma 180 and Ehrlich ascites tumor cells were irradiated in vitro as a 1:10 or 1:1000 suspension in normal saline. During irradiation, metabolism was inhibited by maintaining the cells at 0°C. Dose-effect curves for survival and reproduction were determined during the exponential growth phase (9 days) after intraperitoneal inoculation of approximately 4000 cells. Cells irradiated in low oxygen environment suffered more injury in the diluted (1:1000) than in the more concentrated (1:10) suspension. The results at 9 days were confirmed in their general aspects by ultimate survival (percentage of tumor takes). Dilution of the cell population during exposure was found to be a factor that was distinguishable from that of the oxygen effect.

Chinese hamster ovary cells in monolayer culture, synchronized by mechanically selecting mitotic cells in the absence of drugs, were x-irradiated with 150, 300, or 600 rads at frequent intervals during the cell cycle and examined visually until completion of the first wave of cell division. The synchronized populations consisted of greater than 90% mitotic cells and their subsequent distribution throughout the cycle was carefully documented. At each time-dose combination, growth curves were analyzed for division delay (first, mean, and last cells to divide), the fraction of cells completing the first division, and the duration of the division wave. Results showed that radiation-induced division delay increased exponentially with cell age between early-mid G1 (0.29 minute/rad) and late S-early G2, (0.80 minute/rad) and linearly with dose at any given position in the cell cycle. Mitotic cells were more sensitive than mid- G1 cells (0.43 vs 0.29 minute/rad) and the increase in sensitivity leveled off in G2 a...