Mechanism of intestinal radiosensitization by actinomycin D

The interaction between actinomycin D (Act D) and X-irradiation on the mouse jejunum was examined. The two principal actions of the drug were to: (1) inhibit repair of sublethal radiation damage as evidenced by a reduction in shoulder width of the crypt survival curve and by lack of repair between divided exposures ; and, (2) delay the onset of the compensatory hyperplasia which characteristically occurs following irradiation. Due to the latter, a larger number of surviving crypts was required to provide levels of functional epithelium compatible with animal survival. In experiments employing hydroxyurea to partially synchronize the proliferative compartment, it was found that cells in the G1 phase of the cell cycle were most sensitive to Act D. It was also noted that the majority of crypt cells, exposed to relatively high doses of Act D, were able to ascend the villus. Similar results have been obtained with X irradiation. An interaction between X irradiation and Act D could be detected when the radiation was delivered as long as five days after the drug.