title: Glutathione modifies the oxidation products of 2'-deoxyguanosine by singlet molecular oxygen.
abstract: The oxidation of the free nucleoside 2'-deoxyguanosine (dGuo) by singlet molecular oxygen ((1)O2) has been studied over the three last decades due to the major role of DNA oxidation products in process such as ageing, mutation and carcinogenesis. In the present work we investigated the dGuo oxidation by (1)O2 in the presence of the important low molecular antioxidant, glutathione, in its reduced (GSH) and oxidized (GSSG) forms. There were applied different conditions of concentration, pH, time of incubation, and the use of a [(18)O]-labeled thermolabile endoperoxide naphthalene derivative as a source of [(18)O]-labeled (1)O2. Data was obtained through high performance liquid chromatography (HPLC) and HPLC coupled to micrOTOF Q-II analysis of the main oxidation products: the diastereomers of spiroiminodihydantoin-2'-deoxyribonucleosides (dSp) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). An intriguing result was that 8-oxodGuo levels increased by 100 fold when dGuo was oxidized by (1)O2 in the presence of GSH and by 2 fold in the presence of GSSG, while dSp levels dropped to zero for both conditions. All data from dGuo, 8-oxodGuo and dSp quantification together with the analysis of residual GSH/GSSG content in each sample strongly suggest that glutathione modifies the mechanism of dGuo oxidation by (1)O2 by disfavoring the pathway of dSp formation.
authors.affiliation: Laboratório de Oxidações Biológicas, Departamento de Bioquímica e Biologia Molecular, Setor de Ciências Biológicas, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Patrícia S
authors.initials: PS
authors.lastname: Peres
authors.affiliation: Laboratório de Oxidações Biológicas, Departamento de Bioquímica e Biologia Molecular, Setor de Ciências Biológicas, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Valerio
authors.affiliation: Laboratório de Oxidações Biológicas, Departamento de Bioquímica e Biologia Molecular, Setor de Ciências Biológicas, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Silvia M S C
authors.initials: SM
authors.lastname: Cadena
authors.affiliation: Laboratório de Oxidações Biológicas, Departamento de Bioquímica e Biologia Molecular, Setor de Ciências Biológicas, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Sheila M B
authors.initials: SM
authors.lastname: Winnischofer
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Alexsandra C
authors.initials: AC
authors.lastname: Scalfo
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Mascio
authors.affiliation: Laboratório de Oxidações Biológicas, Departamento de Bioquímica e Biologia Molecular, Setor de Ciências Biológicas, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil. Electronic address: grmartinez@pq.cnpq.br.
authors.forename: Glaucia R
authors.initials: GR
authors.lastname: Martinez
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000737:chemistry / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D008956:Models, Chemical; D010084:Oxidation-Reduction; D026082:Singlet Oxygen / Q000737:chemistry / Q000378:metabolism*; D013141:Spiro Compounds / Q000737:chemistry / Q000378:metabolism
chemical_list: D013141:Spiro Compounds; C408822:spiroiminodihydantoin; D006151:Guanosine; D026082:Singlet Oxygen; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione; D019803:Glutathione Disulfide
keywords: 2′-Deoxyguanosine; 8-Oxo-7,8-dihydro-2′-deoxyguanosine; DNA damage; Glutathione; ROS; Singlet molecular oxygen; Spiroiminodihydantoin-2′-deoxyribonucleosides