Studies on the radiation-sensitizing action of NDPP, a sensitizer of hypoxic cells

While in vitro studies indicate that NDPP is a very efficient sensitizer of hypoxic mammalian cells, studies using the KHT tumor in vivo have failed to produce significant sensitization except when the compound is injected directly into the tumor. In vitro studies, carried out to resolve this apparent discrepancy, indicate that NDPP is itself a rather inefficient sensitizer but undergoes conversion to a more active form. While this conversion occurs more rapidly under basic conditions, the maximum conversion occurs at approximately 2 hr at pH 7.4. The studies reported here suggest that this active form binds to serum and cellular proteins as well as to small sulfhydryl-containing molecules such as glutathione. Based on the evidence presented it is suggested that the active form of NDPP is a dual-action type of sensitizer which acts partly because of its ability to bind SH groups and partly because of its electron affinic nature.