Journal Article

Preferential targeting of oxidative base damage to interucleosomal DNA

Helen Enright, Wesley J. Miller, Rebecca Hays, Robert A. Floyd and Robert P. Hebbel

in Carcinogenesis

Volume 17, issue 5, pages 1175-1177
Published in print May 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.5.1175
Preferential targeting of oxidative base damage to interucleosomal DNA

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The structure of nuclear chromatin may limit the accessibility of carcinogenic agents to DNA. In the case of oxidative DNA strand cleavage mediated by the physiologically relevant iron chelate, iron—ADP, histone-associated nucleosomal DNA is protected while internucleosomal DNA is susceptible to damage. We now find that the distribution of iron—ADP-generated 8-hydroxydeoxyguanosine, a potentially mutagenic oxidative base change, shows relative targeting to internucleosomal sites (3.5-fold increased oxidative modification of internucleosomal compared with nucleosomal DNA as the minimal degree of enrichment). In contrast, iron—EDTA, which generates hydroxyl radical in the ‘fluid phase’, does not target internucleosomal DNA. Thus, physiologic iron chelates may promote site-specific damage and thereby be relevant to mechanisms of irondependent oxidative mutagenesis and carcinogenesis.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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