title: Oxidative damage to 5-methylcytosine in DNA.
abstract: Exposure of pyrimidines of DNA to ionizing radiation under aerobic conditions or oxidizing agents results in attack on the 5,6 double bond of the pyrimidine ring or on the exocyclic 5-methyl group. The primary product of oxidation of the 5,6 double bond of thymine is thymine glycol, while oxidation of the 5-methyl group yields 5-hydroxymethyluracil. Oxidation of the 5,6 double bond of cytosine yields cytosine glycol, which decomposes to 5-hydroxycytosine, 5-hydroxyuracil and uracil glycol, all of which are repaired in DNA by Escherichia coli endonuclease III. We now describe the products of oxidation of 5-methylcytosine in DNA. Poly(dG-[3H]dmC) was gamma-irradiated or oxidized with hydrogen peroxide in the presence of Fe3+ and ascorbic acid. The oxidized co-polymer was incubated with endonuclease III or 5-hydroxymethyluracil-DNA glycosylase, to determine whether repairable products were formed, or digested to 2'-deoxyribonucleosides, to determine the total complement of oxidative products. Oxidative attack on 5-methylcytosine resulted primarily in formation of thymine glycol. The radiogenic yield of thymine glycol in poly(dG-dmC) was the same as that in poly(dA-dT), demonstrating that 5-methylcytosine residues in DNA were equally susceptible to radiation-induced oxidation as were thymine residues.
authors.affiliation: Department of Biology, New York University Graduate School of Arts and Sciences, New York 10003, USA.
authors.forename: S
authors.initials: S
authors.lastname: Zuo
authors.forename: R J
authors.initials: RJ
authors.lastname: Boorstein
authors.forename: G W
authors.initials: GW
authors.lastname: Teebor
mesh_terms: D044503:5-Methylcytosine; D000818:Animals; D002417:Cattle; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000528:radiation effects; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects*; D004249:DNA Damage; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases; D029968:Escherichia coli Proteins; D005720:Gamma Rays; D006868:Hydrolysis; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D011089:Polydeoxyribonucleotides / Q000737:chemistry / Q000528:radiation effects; D014316:Tritium
chemical_list: D029968:Escherichia coli Proteins; D011089:Polydeoxyribonucleotides; D014316:Tritium; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli