Calcium chelator Quin-2 prevents crocidolite-induced DNA strand breakage in human white blood cells

Mutat Res. 1994 Dec 1;311(2):209-15. doi: 10.1016/0027-5107(94)90178-3.


Exposure of human white blood cells to UICC crocidolite asbestos in vitro resulted in the formation of DNA strand breakage in a dose-dependent manner up to a fibre concentration of 100 micrograms/ml. Subsequent incubations with the iron chelator desferrioxamine or the intracellular Ca2+ chelator Quin-2 prevented DNA strand break formation above control incubations. Addition of aurintricarboxylic acid, an endonuclease inhibitor, similarly abolished crocidolite-induced DNA strand breaks in these cells. These results suggest that crocidolite-derived hydroxyl radicals do not directly induce DNA strand breakage in mammalian white blood cells. In order to assess Ca2+ mobilisation from intracellular stores in control and crocidolite-treated cells, the fullness of these stores was measured by treating with thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca(2+)-ATPase. On addition of thapsigargin to fura-2AM-loaded cells treated with crocidolite we demonstrated that the endoplasmic reticulum stores had been depleted as no further Ca2+ was released, unlike control cells. We suggest that strand breakage is caused by a complex set of events involving oxygen free radicals that may disturb intracellular Ca2+ homoeostasis and the breaks are produced by secondary reactions, involving Ca(2+)-mediated enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / pharmacology*
  • Antimutagenic Agents / pharmacology
  • Asbestos, Crocidolite / toxicity*
  • Aurintricarboxylic Acid / pharmacology
  • Calcium / agonists
  • Calcium / metabolism*
  • Chelating Agents / pharmacology*
  • DNA Damage
  • Deferoxamine / pharmacology
  • Free Radicals / metabolism
  • Humans
  • Leukocytes / drug effects
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism


  • Aminoquinolines
  • Antimutagenic Agents
  • Chelating Agents
  • Free Radicals
  • Reactive Oxygen Species
  • Asbestos, Crocidolite
  • Aurintricarboxylic Acid
  • Deferoxamine
  • Quin2
  • Calcium