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Measuring chromosome breaks in patients with thalassemia.
Offer, Tal; Bhagat, Amrita; Lal, Ashutosh; Atamna, Wafa; Singer, Sylvia T; Vichinsky, Elliott P; Kuypers, Frans A; Ames, Bruce N.
Afiliación
  • Offer T; Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
Ann N Y Acad Sci ; 1054: 439-44, 2005.
Article en En | MEDLINE | ID: mdl-16339694
Iron-mediated oxidative stress plays an important role in the pathophysiology of thalassemia. Oxidative stress can cause lesions in DNA, including double-strand breaks. DNA damage, which is a cause of cancer (although not the only one), is recognized as deleterious. Unlike cancer, DNA damage can be assayed easily and relatively inexpensively in humans. In this study, a sensitive micronucleus assay was used to measure the frequency of chromosomal breaks in patients with alpha- and beta-thalassemia. The micronucleus test is based on the observation that a secondary nucleus (micronucleus) is formed around a chromosomal fragment, outside the main nucleus of a dividing cell. Micronuclei are readily apparent in red blood cells (RBCs), which otherwise lack DNA. We combined an immunomagnetic separation technique with single-laser flow cytometry to isolate and analyze reticulocytes in peripheral blood for the presence of micronuclei before these cells are removed by the spleen. Blood samples were obtained from patients with thalassemia and healthy volunteers. After immunomagnetic enrichment of CD71-positive reticulocytes, the cells were stained for micronuclei using the DNA dye 7-aminoactinomycin D (7-AAD) and evaluated by flow cytometry. Our findings indicate that higher levels of micronuclei frequencies are present in thalassemic RBCs.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Reticulocitos / Talasemia / Pruebas de Micronúcleos / Rotura Cromosómica Límite: Child / Humans Idioma: En Revista: Ann N Y Acad Sci Año: 2005 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Reticulocitos / Talasemia / Pruebas de Micronúcleos / Rotura Cromosómica Límite: Child / Humans Idioma: En Revista: Ann N Y Acad Sci Año: 2005 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos