A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles Academic Article uri icon

Overview

MeSH Major

  • Autophagy
  • Cytoplasmic Vesicles
  • Vacuolar Proton-Translocating ATPases

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.

publication date

  • January 15, 2001

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 11212227

Additional Document Info

start page

  • 439

end page

  • 44

volume

  • 61

number

  • 2