THE INHIBITION OF ETOPOSIDE-INDUCED APOPTOSIS BY ZINC IS ASSOCIATED WITH MODULATION OF INTRACELLULAR PH

Apoptosis is associated with DNA fragmentation, usually as a result of the activation of an endonuclease that digests chromatin DNA between the nucleosomes. The identity of the endonuclease is important for understanding the regulation of apoptosis. A Ca2+/Mg2+-dependent endonuclease is often cited as the critical endonuclease. One inhibitor that has been used to implicate this endonuclease is zinc, which inhibits the endonuclease in vitro and also inhibits apoptosis. Deoxyribonuclease II is an alternate endonuclease that could be involved in apoptosis, yet it is not inhibited by zinc. Deoxyribonuclease II is activated by intracellular acidification which occurs during apoptosis. The current experiments show that zinc inhibits the intracellular acidification associated with apoptosis which may be an alternate means by which it inhibits DNA digestion. Hence zinc appears to inhibit both endonucleases in intact cells, so can not be used to specifically implicate either.