Preferential targeting of oxidative base damage to internucleosomal DNA

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

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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 iron-dependent oxidative mutagenesis and carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1175-1177
Number of pages3
JournalCarcinogenesis
Volume17
Issue number5
DOIs
StatePublished - May 1996

Bibliographical note

Funding Information:
We thank L Maidt for technical advice and C.Taubert for preparing the manuscript. Supported in part by National Institutes of Health grants HL30160 and HL37528 (R.P.H.), CA42854 (R A.F.) and IR29CA65021 (H.E.), a University of Minnesota Grant-in-Aid (H.E.) and the Minnesota Medical Foundation.

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