Mode of Radiosensitization of Hypoxic Cells by Furylfuramide

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During the course of surveying electron affinic sensitizers, we found that furylfuramide (AF-2) showed an apparent sensitizing effect in vitro on hypoxic mouse L5178Y cells irradiated with 900 rads of X-rays but it did not sensitize the cells at less than 600 rads. Sensitizing activity of AF-2 was confirmed in vivo by a single dose (3500 rads) of X-rays on mouse mammary carcinoma, though it failed to sensitize the tumor cells when the radiation was given as multiple fractions. These results present an extreme case for hypoxic sensitizers which had no or decreased potency of sensitization in the low dose range around the shoulder region of survival curves for the irradiated cells. Hypoxic cells in tumors have been a problem in radiotherapy because of their high radioresistance. A means to overcome this problem would be the use of electronafiinic compounds such as nitrobenzenes, nitrofurans and nitroimidazoles which are known to act as efficient and specific radiosensitizers on the hypoxic cells. Generally, the mode of sen itization of these compounds are believed to be simply dose modifying and therefore without changing the extrapolation number.
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