The dilution assay technique was used by Powers and Tolmach to investigate the radiation response of a solid subcutaneous lymphosarcoma in the mouse. Survival estimates were made for doses between 2 and 20 Gy (200 and 2000 rad). The results are shown in figure 6.10 in which the dose on a linear scale is plotted against the fraction of surviving cells on a logarithmic scale.
The survival curve for this solid tumor clearly consists of two separate components. The first, up to a dose of about 9 Gy (900 rad), has a slope (d0) of 1.1 Gy. The second has a shallower slope (D0 = 2.6Gy). this biphasic survival curve has a final slope about 2.5 times shallower than the initial portion, which strongly suggests that the tumor consists of two separate groups of cells, one oxygenated and the other hypoxic. If the shallow component of the curve is extrapolated backward to cut the surviving-fraction-axis, it does so at a survival level of about 1%. From this it may be inferred that about 1 % of the clonogenic cells in the tumor were deficient in oxygen.
The response of this tumor to single doses of radiation of various sizes is explained readily on this basis. If 99%of the cells are well oxygenated and 1% hypoxic, the response to lower doses is dominated by killing of the well oxygenated cells.for these doses, the hypoxic cells are depopulated to a negligibly small extent. Once a dose of about 9Gy is exceeded, however, the oxygenated compartment of the tumour is depopulated severely, and the response of the tumor is characteristic of the response of hypoxic cells. The biphasic survival curve was the first unequivocal demonstration that a solid tumor could contain cells sufficiently hypoxic to be protected from cell killing by x-rays but still clonogenic and capable of providing a focus for tumor regrowth.
The survival curve for this solid tumor clearly consists of two separate components. The first, up to a dose of about 9 Gy (900 rad), has a slope (d0) of 1.1 Gy. The second has a shallower slope (D0 = 2.6Gy). this biphasic survival curve has a final slope about 2.5 times shallower than the initial portion, which strongly suggests that the tumor consists of two separate groups of cells, one oxygenated and the other hypoxic. If the shallow component of the curve is extrapolated backward to cut the surviving-fraction-axis, it does so at a survival level of about 1%. From this it may be inferred that about 1 % of the clonogenic cells in the tumor were deficient in oxygen.
The response of this tumor to single doses of radiation of various sizes is explained readily on this basis. If 99%of the cells are well oxygenated and 1% hypoxic, the response to lower doses is dominated by killing of the well oxygenated cells.for these doses, the hypoxic cells are depopulated to a negligibly small extent. Once a dose of about 9Gy is exceeded, however, the oxygenated compartment of the tumour is depopulated severely, and the response of the tumor is characteristic of the response of hypoxic cells. The biphasic survival curve was the first unequivocal demonstration that a solid tumor could contain cells sufficiently hypoxic to be protected from cell killing by x-rays but still clonogenic and capable of providing a focus for tumor regrowth.
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