TY - JOUR
T1 - Mitotic delay in lymphocytes from BRCA1 heterozygotes unable to reduce the radiation-induced chromosomal damage
AU - Febrer, Emma
AU - Mestres, Marta
AU - Rosa Caballín, María
AU - Barrios, Leonardo
AU - Ribas, Montserrat
AU - Gutiérrez-Enríquez, Sara
AU - Alonso, Carmen
AU - Ramón y Cajal, Teresa
AU - Francesc Barquinero, Joan
N1 - Funding Information:
This work received financial support from the Consejo de Seguridad Nuclear (CSN-E-978/04). The sponsor had no role in study design, data collection, analysis or interpretation. M.M., M.R.C., L.B., J.F.B., are from group of investigation of the Generalitat de Catalunya (2005 SGR 00164).
PY - 2008/11/1
Y1 - 2008/11/1
N2 - 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 G2 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 G2 and M phase cells, and to evaluate the G2-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 G2 cells in BRCA1+/- was significantly higher than in BRCA1+/+, indicating a higher G2 delay after IR exposure in cells from BRCA1+/- females. On the other hand, whereas the mean frequency of chromatid breaks (chtb) in G2 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 G2 delay of BRCA1+/- more damaged cells are able to pass the G2-to-M transition.
AB - 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 G2 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 G2 and M phase cells, and to evaluate the G2-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 G2 cells in BRCA1+/- was significantly higher than in BRCA1+/+, indicating a higher G2 delay after IR exposure in cells from BRCA1+/- females. On the other hand, whereas the mean frequency of chromatid breaks (chtb) in G2 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 G2 delay of BRCA1+/- more damaged cells are able to pass the G2-to-M transition.
KW - BRCA1
KW - Chromatid breaks
KW - Heterozygotes
KW - Premature chromosome condensation
KW - Radiation-induced DSB
UR - http://www.scopus.com/inward/record.url?scp=53149084440&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2008.08.001
DO - 10.1016/j.dnarep.2008.08.001
M3 - Article
AN - SCOPUS:53149084440
SN - 1568-7864
VL - 7
SP - 1907
EP - 1911
JO - DNA Repair
JF - DNA Repair
IS - 11
ER -