title: G2 checkpoint-dependent DNA repair and its response to catalase in Down syndrome and control lymphocyte cultures.
abstract: The amount of DNA lesions repaired in G2 and also G2 timing are controlled by the DNA damage-dependent checkpoint. Down syndrome (DS) lymphocytes showed twice as much constitutive DNA damage in G2 than control ones, when recording it as chromosomal aberrations in metaphase, after caffeine-induced checkpoint abrogation. During G2, DS lymphocytes repaired 1.5 times more DNA lesions than control ones. However the DS cells displayed a decreased threshold for checkpoint adaptation, as the spontaneous override of the G2 to mitosis transition block induced by the checkpoint took place in the DS cells when they had three times more DNA lesions than controls. Catalase addition to cultures scavenges hydrogen peroxide diffused from cells, resulting in subsequent intracellular depletion (Antunes and Cadenas, 2000). The intracellular H2O2 level seemed to regulate the G2 checkpoint. Thus, in controls, H2O2 depletion (induced by 3.2-50 microg/mL catalase) prevented its functioning: chromosomal damage increased while G2 shortened. Conversely, in the DS lymphocytes, 12.5 microg/mL catalase lengthened G2 and decreased chromosomal damage, in spite that the amount of DNA repaired in G2 was half of that repaired in the catalase-free DS lymphocytes.
authors.affiliation: Programa de Genética Humana-ICBM, Facultad de Medicina, Universidad de Chile, Casilla 70061, Santiago 7, Chile.
authors.forename: Juana
authors.initials: J
authors.lastname: Pincheira
authors.forename: Pablo
authors.initials: P
authors.lastname: Romero
authors.forename: Katherine
authors.initials: K
authors.lastname: Marcelain
authors.forename: Lorena
authors.initials: L
authors.lastname: Salazar
authors.forename: Consuelo
authors.initials: C
authors.lastname: de la Torre
mesh_terms: D002110:Caffeine / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D004314:Down Syndrome / Q000473:pathology*; D005260:Female; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D013997:Time Factors
chemical_list: D002110:Caffeine; D002374:Catalase