MICROMOLAR ZINC AFFECTS ENDONUCLEOLYTIC ACTIVITY IN HYDROGEN PEROXIDE-MEDIATED APOPTOSIS

When damaged by hydrogen peroxide, peripheral blood lymphocytes underg o cell death by apoptosis in the absence of internucleosomal DNA cleav age, while, in the same cells, other apoptosis-inducing treatments bri ng DNA cleavage to completion. However, the formation of internucleoso mal DNA fragments is readily obtained if cells are pretreated with a d ivalent metal chelator, TPEN, at micromolar concentrations. Since the coadministration of equimolar zinc concentrations abrogates the format ion of the ladder, a zinc-inhibitable endonucleolytic activity is acco unted for the effect. Most notably, subtraction of zinc ions does not increase the percentage of cells undergoing apoptosis, bur rather resu lts in a rescue form death. (C) 1998 Academic Press.