title: DNA damage in Fabry patients: An investigation of oxidative damage and repair.
abstract: Fabry disease (FD) is a lysosomal storage disorder associated with loss of activity of the enzyme α-galactosidase A. In addition to accumulation of α-galactosidase A substrates, other mechanisms may be involved in FD pathophysiology, such as inflammation and oxidative stress. Higher levels of oxidative damage to proteins and lipids in Fabry patients were previously reported. However, DNA damage by oxidative species in FD has not yet been studied. We investigated basal DNA damage, oxidative DNA damage, DNA repair capacity, and reactive species generation in Fabry patients and controls. To measure oxidative damage to purines and pyrimidines, the alkaline version of the comet assay was used with two endonucleases, formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). To evaluate DNA repair, a challenge assay with hydrogen peroxide was performed. Patients presented significantly higher levels of basal DNA damage and oxidative damage to purines. Oxidative DNA damage was induced in both DNA bases by H2O2 in patients. Fabry patients presented efficient DNA repair in both assays (with and without endonucleases) as well as significantly higher levels of oxidative species (measured by dichlorofluorescein content). Even if DNA repair be induced in Fabry patients (as a consequence of continuous exposure to oxidative species), the repair is not sufficient to reduce DNA damage to control levels.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Giovana Brondani
authors.initials: GB
authors.lastname: Biancini
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre (UFSCPA), Porto Alegre, RS, Brazil.
authors.forename: Dinara Jaqueline
authors.initials: DJ
authors.lastname: Moura
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre (UFSCPA), Porto Alegre, RS, Brazil.
authors.forename: Paula Regina
authors.initials: PR
authors.lastname: Manini
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Jéssica Lamberty
authors.initials: JL
authors.lastname: Faverzani
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Cristina Brinckmann Oliveira
authors.initials: CB
authors.lastname: Netto
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Marion
authors.initials: M
authors.lastname: Deon
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre (UFSCPA), Porto Alegre, RS, Brazil.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Saffi
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address: crvargas@hcpa.edu.br.
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
mesh_terms: D000328:Adult; D000368:Aged; D004249:DNA Damage; D004260:DNA Repair; D000795:Fabry Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species; D055815:Young Adult
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide
keywords: DNA damage; DNA repair; Fabry disease; Oxidative stress; Reactive species