US EPA

3081720 

Journal Article 

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

Faux, SP; Michelangeli, F; Levy, LS 

1994 

1 

Mutation Research
ISSN: 0027-5107
EISSN: 1873-135X 

ELSEVIER SCIENCE BV 

AMSTERDAM 

NIOSH/00224891 

311 

2 

209-215 

English 

7526185 

10.1016/0027-5107(94)90178-3 

WOS:A1994PU12300005 

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. 

Aminoquinolines; Antimutagenic Agents; Chelating Agents; Free Radicals; Reactive Oxygen Species; Asbestos, Crocidolite; 12001-28-4; Aurintricarboxylic Acid; 4431-00-9; Deferoxamine; J06Y7MXW4D; O448IDK23O; Calcium; SY7Q814VUP; Index Medicus; Leukocytes -- drug effects; Aurintricarboxylic Acid -- pharmacology; Deferoxamine -- pharmacology; Reactive Oxygen Species -- metabolism; Antimutagenic Agents -- pharmacology; Free Radicals -- metabolism; DNA Damage; Chelating Agents -- pharmacology; Oxidative Stress; Calcium -- agonists; Calcium -- metabolism; Aminoquinolines -- pharmacology; Asbestos, Crocidolite -- toxicity