A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles

The mechanisms underlying neoplastic epithelial cell killing by ionizing ra diation are largely unknown, We discovered a novel response to radiation ma nifested by autophagy and the development of acidic vesicular organelles (A VO), Acidification of AVO was mediated by the vacuolar Hf-ATPase, Staining with the lysosomotropic agent acridine orange enabled us to quantify AVO ac cumulation and to demonstrate their time- and dose-dependent appearance, Th e appearance of AVO occurred in the presence of the pan-caspase inhibitor z -Val-Ala-Asp(Ome)-fluoromethyl ketone, but was inhibited by 3-methyladenine , an inhibitor of autophagy, The accretion of AVO in surviving progenies of irradiated cells, and the increased incidence of clonogenic death after in hibition of vacuolar H+-ATPase suggest that formation of acidic organelles represents a novel defense mechanism against radiation damage.