title: Mitotic delay in lymphocytes from BRCA1 heterozygotes unable to reduce the radiation-induced chromosomal damage.
abstract: 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.
authors.affiliation: Unitat d'Antropologia Biològica, Departament de Biologia Animal, Biologia Vegetal i Ecología, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Febrer
authors.forename: Marta
authors.initials: M
authors.lastname: Mestres
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Caballín
authors.forename: Leonardo
authors.initials: L
authors.lastname: Barrios
authors.forename: Montserrat
authors.initials: M
authors.lastname: Ribas
authors.forename: Sara
authors.initials: S
authors.lastname: Gutiérrez-Enríquez
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.forename: Teresa
authors.initials: T
authors.lastname: Ramón y Cajal
authors.forename: Joan
authors.initials: J
authors.lastname: Francesc Barquinero