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1.
DNA Repair (Amst) ; 7(11): 1907-11, 2008 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-18765304

RESUMEN

Double strand breaks (DSB) are critical lesions involved in the formation of chromosomal aberrations. In response to DNA damage, the cell has mechanisms of repair and cell-cycle control to maintain the genome integrity in which BRCA1 gene is implicated. In the present study an evaluation of the radio-induced damage in G(2) phase of the cell cycle in lymphocytes from BRCA1 heterozygotes is presented. For this purpose Calyculin-A-based premature chromosome condensation (PCC) combined with mitotic arrest has been applied to examine with conventional cytogenetics the damage in G(2) and M phase cells, and to evaluate the G(2)-to-M phase transition. Irradiated peripheral blood lymphocytes from seven heterozygote females (BRCA1(+/-)) and seven control females (BRCA1(+/+)) have been analyzed. The mean proportion of G(2) cells in BRCA1(+/-) was significantly higher than in BRCA1(+/+), indicating a higher G(2) delay after IR exposure in cells from BRCA1(+/-) females. On the other hand, whereas the mean frequency of chromatid breaks (chtb) in G(2) cells was not statistically different between both groups, the mean frequency of chtb in M cells of the BRCA1(+/-) group was significantly higher than in the BRCA1(+/+) one. Moreover, the mean proportion of M cells with aberrations was significantly higher in BRCA1(+/-) than in BRCA1(+/+) suggesting that in spite of the higher G(2) delay of BRCA1(+/-) more damaged cells are able to pass the G(2)-to-M transition.


Asunto(s)
Proteína BRCA1/genética , Cromosomas/efectos de la radiación , Daño del ADN , Heterocigoto , Mitosis , Animales , Ciclo Celular , División Celular , Cromosomas/ultraestructura , Demecolcina/farmacología , Femenino , Fase G2 , Linfocitos/metabolismo , Toxinas Marinas , Ratones , Modelos Biológicos , Oxazoles/farmacología
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