Micromolar Zinc Affects Endonucleolytic Activity in Hydrogen Peroxide-Mediated Apoptosis

When damaged by hydrogen peroxide, peripheral blood lymphocytes undergo cell death by apoptosis in the absence of internucleosomal DNA cleavage, while, in the same cells, other apoptosis-inducing treatments bring DNA cleavage to completion. However, the formation of internucleosomal DNA fragments is readily obtained if cells are pretreated with a divalent metal chelator, TPEN, at micromolar concentrations. Since the coadministration of equimolar zinc concentrations abrogates the formation of the ladder, a zinc-inhibitable endonucleolytic activity is accounted for the effect. Most notably, subtraction of zinc ions does not increase the percentage of cells undergoing apoptosis, but rather results in a rescue from death.