E. Clementi et al., THE INOSITOL 1,4,5-TRISPHOSPHATE-GENERATING AGONIST ATP ENHANCES DNA CLEAVAGE INDUCED BY TERT-BUTYLHYDROPEROXIDE, Experimental cell research, 239(1), 1998, pp. 175-178
In this paper we present experimental evidence indicating that DNA cle
avage induced by tert-butylhydroperoxide in U937 cells can be enhanced
via ATP-mediated activation of membrane receptors coupled with hydrol
ysis of phosphatidylinositol 4,5-bisphosphate. The mechanism whereby A
TP exerts this effect involves release of Ca2+ from the inositol 1,4,5
-trisphosphate (IP3)-sensitive stores, further release of the cation f
rom the ryanodine receptor, mitochondrial clearance of the fraction of
Ca2+ derived from the ryanodine receptor, and Ca2+-dependent mitochon
drial formation of DNA-damaging species. IP3-generating agonists must
therefore be considered as potential modulators of the genotoxic effec
ts of tert-butylhydroperoxide. (C) 1998 Academic Press.