title: Homocysteine contribution to DNA damage in cystathionine β-synthase-deficient patients.
abstract: High blood levels of homocysteine (Hcy) are found in patients affected by homocystinuria, a genetic disorder caused by deficiency of cystathionine β-synthase (CBS) activity, as well as in nutritional deficiencies (vitamin B12 or folate) and in abnormal renal function. We previously demonstrated that lipid and protein oxidative damage is increased and the antioxidant defenses diminished in plasma of CBS-deficient patients, indicating that oxidative stress is involved in the pathophysiology of this disease. In the present work, we extended these investigations by evaluating DNA damage through the comet assay in peripheral leukocytes from CBS-deficient patients, as well as by analyzing of the in vitro effect of Hcy on DNA damage in white blood cells. We verified that DNA damage was significantly higher in the CBS-deficient patients under treatment based on a protein-restricted diet and pyridoxine, folic acid, betaine and vitamin B12 supplementation, when compared to controls. Furthermore, the in vitro study showed a concentration-dependent effect of Hcy inducing DNA damage. Taken together, the present data indicate that DNA damage occurs in treated CBS-deficient patients, possibly due to high Hcy levels.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica da Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos 2700, Porto Alegre, RS 90035-000, Brazil; Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Porto Alegre, RS 90035-903, Brazil. Electronic address: cami_vanzin@hotmail.com.
authors.forename: Camila Simioni
authors.initials: CS
authors.lastname: Vanzin
authors.affiliation: Programa de Pós-Graduação em Bioquímica da Universidade Federal do Pampa (UNIPAMPA), BR 472, Km 585, Uruguaiana, RS 97500-970, Brazil.
authors.forename: Vanusa
authors.initials: V
authors.lastname: Manfredini
authors.affiliation: Programa de Pós-Graduação em Bioquímica da Universidade Federal do Pampa (UNIPAMPA), BR 472, Km 585, Uruguaiana, RS 97500-970, Brazil.
authors.forename: Ana Eveline
authors.initials: AE
authors.lastname: Marinho
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica da Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos 2700, Porto Alegre, RS 90035-000, Brazil; Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Porto Alegre, RS 90035-903, Brazil.
authors.forename: Giovana Brondani
authors.initials: GB
authors.lastname: Biancini
authors.affiliation: Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Porto Alegre, RS 90035-903, Brazil.
authors.forename: Graziela Schmitt
authors.initials: GS
authors.lastname: Ribas
authors.affiliation: Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Porto Alegre, RS 90035-903, Brazil.
authors.forename: Marion
authors.initials: M
authors.lastname: Deon
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica da Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos 2700, Porto Alegre, RS 90035-000, Brazil.
authors.forename: Angela Terezinha de Souza
authors.initials: AT
authors.lastname: Wyse
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica da Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos 2700, Porto Alegre, RS 90035-000, Brazil; Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Porto Alegre, RS 90035-903, Brazil.
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica da Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos 2700, Porto Alegre, RS 90035-000, Brazil; Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Porto Alegre, RS 90035-903, Brazil.
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D020552:Comet Assay; D003541:Cystathionine beta-Synthase / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D004249:DNA Damage; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood*; D006712:Homocystinuria / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D011379:Prognosis; D055815:Young Adult
chemical_list: D006710:Homocysteine; D003541:Cystathionine beta-Synthase
keywords: Comet assay; DNA damage; Homocysteine; Homocystinuria