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 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.