Radiation Response of the Cells of a Human Malignant Melanoma Xenograft. Effect of Hypoxic Cell Radiosensitizers

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Abstract
The radiation response of the cells of E. E. malignant melanoma [human cells] irradiated in suspension in vitro and as solid tumors in the athymic nude mouse was studied. The dose-response curves for cells irradiated in vitro under aerobic (D0 = 0.88 .+-. 0.11 Gy [gray], n = .**GRAPHIC**. and extremely hypoxic (D0 = 2.52 .+-. 0.17 Gy, n = .**GRAPHIC**. conditions indicated that the cells have a considerable capacity for accumulations of sublethal damage. The terminal slope of the dose-response curves for tumors irradiated in air-breathing (D0 = 2.27 .+-. 0.19 Gy) or dead (D0 = 2.47 .+-. 0.23 Gy) mice was not significantly different from that measured for extremely hypoxic cells irradiated in vitro. The shoulder of the dose-response curve for cells irradiated as tumors in dead mice (n = .**GRAPHIC**. was at least as large as that for cells irradiated in suspension under extremely hypoxic conditions. By assuming that acute and chronically hypoxic cells showed the same response to irradiation, the fraction of hypoxic cells in the tumors was determined to be 5-10%. The D0 value for the hypoxic cells in tumors irradiated in air-breathing mice was increased by a factor of .apprx. 1.3 when the tumors were removed 14 h after irradiation instead of immediately afterward. This is probably due to the repair of potentially lethal damage. The radiation response of the tumors was enhanced when the hypoxic cell radiosensitizers misonidazole and Ro-07-0741 were present during irradiation. No significant difference in the potentiating effect of these 2 radiosensitizers was observed. The data indicated that the enhancement ratios for these drugs measured when the tumors were removed and assayed in vitro were somewhat higher than those measured when the tumors were left in situ and tumor regrowth delay was used as the measure of response. The presence of misonidazole and Ro-07-0741 during irradiation did not significantly change the capacity of the hypoxic cells to repair potentially lethal damage.