NOVEL CONCEPTS IN MODIFICATION OF RADIATION SENSITIVITY

Purpose: To determine whether biological effects of radiation, such as apoptosis, that differ from classical clonogenic cell killing, can be modified with agents that would not be expected to modify classical c lonogenic cell killing. This would expand the range of potential modif iers of radiation therapy. Methods and Materials: EL4 murine lymphoma cell apoptosis was determined by electrophoretic analysis of deoxyribo nucleic acid (DNA) fragmentation. DNA was extracted 24 h after irradia tion or addition of inducing agents. Modifiers of radiation-induced ap optosis were added immediately after irradiation. The effects of radia tion on wounded endothelial monolayers were studied by scraping a line across the monolayer 30 min after irradiation. Cell detachment was us ed as an endpoint to determine the protective effect of prolonged expo sure to retinol prior to irradiation. Results: EL4 cell apoptosis can be induced by tert-butyl hydroperoxide or the glutathione oxidant SR-4 077. Radiation-induced EL4 cell apoptosis can be inhibited with 3-amin obenzamide, an agent that sensitizes cells to classical clonogenic cel l killing. Radiation-induced endothelial cell detachment from confluen t monolayers can be modified by pretreatment with retinol. Conclusion: These results raise the possibility that radiation could induce apopt osis by an oxidative stress mechanism that is different from that invo lved in classical clonogenic cell killing. These and other recent find ings encourage the notion that differential modification of classical clonogenic cell killing and other important endpoints of radiation act ion may be possible.