title: Hydroxyl radical induced cross-linking of cytosine and tyrosine in nucleohistone.
abstract: Hydroxyl radical induced formation of a DNA-protein cross-link involving cytosine and tyrosine in nucleohistone in buffered aqueous solution is reported. The technique of gas chromatography-mass spectrometry was used for this investigation. A gamma-irradiated aqueous mixture of cytosine and tyrosine was first investigated in order to obtain gas chromatographic-mass spectrometric properties of possible cytosine-tyrosine cross-links. One cross-link was observed, and its structure was identified as the product from the formation of a covalent bond between carbon 6 of cytosine and carbon 3 of tyrosine. With the use of gas chromatography-mass spectrometry with selected-ion monitoring, this cytosine-tyrosine cross-link was identified in acidic hydrolysates of calf thymus nucleohistone gamma-irradiated in N2O-saturated aqueous solution. The yield of this DNA-protein cross-link in nucleohistone was found to be a linear function of the radiation dose in the range of 100-500 Gy (J.kg-1). This yield amounted to 0.05 nmol.J-1. Mechanisms underlying the formation of the cytosine-tyrosine cross-link in nucleohistone were proposed to involve radical-radical and/or radical addition reactions of hydroxyl adduct radicals of cytosine and tyrosine moieties, forming a covalent bond between carbon 6 of cytosine and carbon 3 of tyrosine. When oxygen was present in irradiated solutions, no cytosine-tyrosine cross-links were observed.
authors.affiliation: Center for Chemical Technology, National Institute of Standards and Technology, Gaithersburg, Maryland 20899.
authors.forename: E
authors.initials: E
authors.lastname: Gajewski
authors.forename: M
authors.initials: M
authors.lastname: Dizdaroglu
mesh_terms: D000818:Animals; D002417:Cattle; D003432:Cross-Linking Reagents; D003596:Cytosine / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005720:Gamma Rays; D008401:Gas Chromatography-Mass Spectrometry; D006657:Histones / Q000378:metabolism*; D006878:Hydroxides / Q000494:pharmacology*; D017665:Hydroxyl Radical; D011485:Protein Binding; D013950:Thymus Gland / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D006657:Histones; D006878:Hydroxides; D017665:Hydroxyl Radical; D014443:Tyrosine; D003596:Cytosine; D004247:DNA