Mitotic delay in lymphocytes from BRCA1 heterozygotes unable to reduce the radiation-induced chromosomal damage

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.