PMID- 22725252
OWN - NLM
STAT- MEDLINE
DCOM- 20130129
LR  - 20131121
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 25
IP  - 9
DP  - 2012 Sep 17
TI  - Profiling cytosine oxidation in DNA by LC-MS/MS.
PG  - 1902-11
LID - 10.1021/tx300195f [doi]
AB  - Spontaneous and oxidant-induced damage to cytosine is probably the main cause of 
      CG to TA transition mutations in mammalian genomes. The reaction of hydroxyl 
      radical (.OH) and one-electron oxidants with cytosine derivatives produces 
      numerous oxidation products, which have been identified in large part by model 
      studies with monomers and short oligonucleotides. Here, we developed an 
      analytical method based on LC-MS/MS to detect 10 oxidized bases in DNA, including 
      5 oxidation products of cytosine. The utility of this method is demonstrated by 
      the measurement of base damage in isolated calf thymus DNA exposed to ionizing 
      radiation in aerated aqueous solutions (0-200 Gy) and to well-known Fenton-like 
      reactions (Fe(2+) or Cu(+) with H(2)O(2) and ascorbate). The following cytosine 
      modifications were quantified as modified 2'-deoxyribonucleosides upon exposure 
      of DNA to ionizing radiation in aqueous aerated solution: 5-hydroxyhydantoin 
      (Hyd-Ura) > 5-hydroxyuracil (5-OHUra) > 5-hydroxycytosine (5-OHCyt) > 
      5,6-dihydroxy-5,6-dihydrouracil (Ura-Gly) > 
      1-carbamoyl-4,5-dihydroxy-2-oxoimidazolidine (Imid-Cyt). The total yield of 
      cytosine oxidation products was comparable to that of thymine oxidation products 
      (5,6-dihydroxy-5,6-dihydrothymine (Thy-Gly), 5-hydroxy-5-methylhydantotin 
      (Hyd-Thy), 5-(hydroxymethyl)uracil (5-HmUra), and 5-formyluracil (5-ForUra)) as 
      well as the yield of 8-oxo-7,8-dihydroguanine (8-oxoGua). The major oxidation 
      product of cytosine in DNA was Hyd-Ura. In contrast, the formation of Imid-Cyt 
      was a minor pathway of DNA damage, although it is the major product arising from 
      irradiation of the monomers, cytosine, and 2'-deoxycytidine. The reaction of 
      Fenton-like reagents with DNA gave a different distribution of cytosine derived 
      products compared to ionizing radiation, which likely reflects the reaction of 
      metal ions with intermediate peroxyl radicals or hydroperoxides. The analysis of 
      the main cytosine oxidation products will help elucidate the complex mechanism of 
      oxidative degradation of cytosine in DNA and probe the consequences of these 
      reactions in biology and medicine.
FAU - Samson-Thibault, Francois
AU  - Samson-Thibault F
AD  - Departement de Medecine nucleaire et Radiobiologie, Faculte de Medecine, 3001 12e 
      Avenue Nord, Universite de Sherbrooke, Quebec, Canada J1H 5N4.
FAU - Madugundu, Guru S
AU  - Madugundu GS
FAU - Gao, Shanshan
AU  - Gao S
FAU - Cadet, Jean
AU  - Cadet J
FAU - Wagner, J Richard
AU  - Wagner JR
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120716
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Fenton's reagent)
RN  - 0 (Nitrogen Isotopes)
RN  - 8J337D1HZY (Cytosine)
RN  - 9007-49-2 (DNA)
RN  - 91080-16-9 (calf thymus DNA)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - *Chromatography, High Pressure Liquid
MH  - Cytosine/*analogs & derivatives/analysis
MH  - DNA/*chemistry/metabolism
MH  - DNA Damage
MH  - Hydrogen Peroxide/chemistry
MH  - Iron/chemistry
MH  - Nitrogen Isotopes/chemistry
MH  - Oxidation-Reduction
MH  - Radiation, Ionizing
MH  - *Tandem Mass Spectrometry
EDAT- 2012/06/26 06:00
MHDA- 2013/01/30 06:00
CRDT- 2012/06/26 06:00
PHST- 2012/06/26 06:00 [entrez]
PHST- 2012/06/26 06:00 [pubmed]
PHST- 2013/01/30 06:00 [medline]
AID - 10.1021/tx300195f [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2012 Sep 17;25(9):1902-11. doi: 10.1021/tx300195f. Epub 2012 
      Jul 16.