title: Evidence that DNA damage is associated to phenylalanine blood levels in leukocytes from phenylketonuric patients.
abstract: Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism, biochemically characterized by the accumulation of Phe and its metabolites in blood and tissues of affected patients. Treatment for PKU consists of a protein restricted diet supplemented with a mixture containing essential amino acids (other than Phe) and micronutrients. In recent years several authors have studied the pathomechanisms of the disease and demonstrated the existence of lipid and protein oxidative damage in PKU patients. In this work we investigated the in vivo and in vitro effects of Phe on DNA damage determined by the alkaline comet assay using silver staining and visual scoring. We found a dose-dependent effect of Phe on DNA damage in leukocytes from normal individuals incubated with different concentrations of Phe. Additionally, by analyzing blood leukocytes from two groups of treated PKU patients based on their blood Phe levels, we verified that the DNA damage index was significantly higher in PKU patients with high Phe blood levels (DI = 68.2 +/- 12.3), compared to well-treated patients and the control group (healthy individuals). Furthermore, well-treated PKU patients had greater DNA damage (DI = 44.9 +/- 7.6) relatively to controls (DI = 12.7 +/- 4.1). Our present in vitro and in vivo findings indicate that DNA damage occurs in peripheral blood from PKU patients and is associated to Phe blood levels.
authors: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, CEP 90035-003, Porto Alegre, RS, Brazil. angelasitta@yahoo.com.br
authors: Angela
authors: A
authors: Sitta
authors: Vanusa
authors: V
authors: Manfredini
authors: Lidiana
authors: L
authors: Biasi
authors: Roberta
authors: R
authors: Treméa
authors: Ida V D
authors: IV
authors: Schwartz
authors: Moacir
authors: M
authors: Wajner
authors: Carmen R
authors: CR
authors: Vargas
mesh_terms: D002675:Child, Preschool; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D019587:Dietary Supplements; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000378:metabolism; D018384:Oxidative Stress; D010649:Phenylalanine / Q000097:blood* / Q000494:pharmacology*; D010661:Phenylketonurias / Q000097:blood*
chemical_list: D010649:Phenylalanine