Correlation between Mitotic Delay and Micronucleus Assay in Breast cancer patients

Abstract

Breast cancer has been associated with a variety of mutations in susceptibility genes. These patients also exhibit impaired DNA repair capacity when compared to controls, which has been assessed by different tests measuring the ability to repair DNA damage. Yet unanswered is the question if those tests produce correlated results on an individual basis. For this purpose, micronucleus test (MNT) and mitotic delay assay were performed simultaneously on the same probands. Blood samples were obtained from 46 probands. Micronucleus test was performed with spontaneous or radiation-induced lymphocyte cultures (2Gy at setup). Samples for mitotic delay were irradiated after 54h, 18h prior to measurement. Mitotic delay index was calculated as (ratio [cells G2-phase]/[cells S-phase] of irradiated cultures divided by G2/S ratio of control cultures). There was no correlation of spontaneous MN frequencies to radiation-induced MN frequencies (p=0.38). While there was also no correlation between mitotic delay index and spontaneous MN frequencies (p=0.78), we did observe a statistically significant correlation between mitotic delay index and induced MN-frequencies (p=0.04) As both increased mitotic delay index and radiation induced micronucleus frequencies are known to be associated with defects in DNA damage repair and with breast cancer, the presence of correlation between these both tests indicates that the produced results characterize DNA repair capacity in a similar way. Thus they seem to measure linked aspects of DNA damage response. A combined approach using these tests could prove to be a useful step towards increased significance when screening patients for a phenotype of decreased DNA repair.