A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles Journal Article
| Authors: | Paglin, S.; Hollister, T.; Delohery, T.; Hackett, N.; McMahill, M.; Sphicas, E.; Domingo, D.; Yahalom, J. |
| Article Title: | A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles |
| Abstract: | The mechanisms underlying neoplastic epithelial cell killing by ionizing radiation are largely unknown. We discovered a novel response to radiation manifested by autophagy and the development of acidic vesicular organelles (AVO). Acidification of AVO was mediated by the vacuolar H+-ATPase. Staining with the lysosomotropic agent acridine orange enabled us to quantify AVO accumulation and to demonstrate their time- and dose-dependent appearance. The 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 inhibition of vacuolar H+-ATPase suggest that formation of acidic organelles represents a novel defense mechanism against radiation damage. |
| Keywords: | controlled study; human cell; microscopy, electron; tumor cells, cultured; caspase inhibitor; radiation injury; radiation response; time factors; dose-response relationship, radiation; cancer cell; dna, neoplasm; ionizing radiation; autophagy; acridine orange; cell organelle; cell killing; hydrogen-ion concentration; adenine; dose time effect relation; acidification; cytoplasmic vesicles; vacuolar proton-translocating atpases; humans; human; priority journal; article; 3 methyladenine; proton-translocating atpases; defense mechanism; proton transporting adenosine triphosphatase |
| Journal Title: | Cancer Research |
| Volume: | 61 |
| Issue: | 2 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2001-01-15 |
| Start Page: | 439 |
| End Page: | 444 |
| Language: | English |
| PUBMED: | 11212227 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
