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.
CITATION STYLE
Enright, H., Miller, W. J., Hays, R., Floyd, R. A., & Hebbel, R. P. (1996). Preferential targeting of oxidative base damage to internucleosomal DNA. Carcinogenesis, 17(5), 1175–1177. https://doi.org/10.1093/carcin/17.5.1175
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