A number of clinical factors have been noted to decrease sensitivity of tumors to the effects of ionizing radiation. Which of the following is most important in this regard?

c. Tissue hypoxia

The radiosensitivity of cells depends on their position within the cell cycle. Cells in the M phase (mitotic phase) are most sensitive. At the time of any given dose, only a fraction of cells will be in a vulnerable position within the cell cycle. Subsequently, the sensitivity of the tumor versus normal tissue depends on the ability of cells to redistribute and repopulate within the radiated volume. In tumors that are particularly radiosensitive, this balance between cell killing and repopulation favors the normal tissues over the tumor. The ability to recruit cells from adjacent undamaged areas should also favor normal tissues.

 The presence or absence of molecular oxygen greatly influences the proportion of cells killed by a given dose of radiation. The availability of oxygen is clearly the most important factor for enhancing the formation and prolonging the survival of free radicals. Therefore, radiosensitivity of cells within a given tumor varies based on their location relative to oxygencarrying capillaries. Cells in hypoxic regions of a tumor may escape the effects of radiation. As conditions change with progressive cell killing, fewer cells theoretically exist in hypoxic regions, and oxygen may become more evenly distributed within the tumor volume.