title: Preferential targeting of oxidative base damage to internucleosomal DNA.
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.
authors.affiliation: Department of Medicine, University of Minnesota Medical Center, Minneapolis 55455, USA.
authors.forename: H
authors.initials: H
authors.lastname: Enright
authors.forename: W J
authors.initials: WJ
authors.lastname: Miller
authors.forename: R
authors.initials: R
authors.lastname: Hays
authors.forename: R A
authors.initials: RA
authors.lastname: Floyd
authors.forename: R P
authors.initials: RP
authors.lastname: Hebbel
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology; D009707:Nucleosomes / Q000187:drug effects*; D010084:Oxidation-Reduction
chemical_list: D007502:Iron Chelating Agents; D009707:Nucleosomes; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine