INTRACELLULAR CA-2+ CHELATORS PREVENT DNA DAMAGE AND PROTECT HEPATOMA 1C1C7 CELLS FROM QUINONE-INDUCED CELL KILLING

Exposure of hepatoma lclc7 cells to 2,3-drniethoxy-1.4-naphthoquinone (DMNQ) resulted in a sustained elevation of cytosolic Ca2+. DNA single strand breaks and cell killing. DNA single strand break formation was prevented when cells were preloaded with either of the intracellular Ca2+ chelators. Quin 2 or BAPTA, to buffer the increase in cytosolic Ca2+ concentration induced by the quinone. DMNQ caused marked NAD+ depletion which was prevented when cells were preincubated with 3-aminobenzamide. an inhibitor of nuclear poly-(ADP-ribose)-synthetase activity. or with either of the two Ca2+ chelators. However. 3-aminobenzamide did not protect the hepatoma cells from loss of viability. Our results indicate that quinone-induced DNA damage. NAD+ depletion and cell killing are mediated by a sustained elevation of cytosolic Ca2+ © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.