Correlation between DNA double strand breaks and cell death in peripheral blood lymphocytes from breast cancer patients

Abstract

Radiotherapy is an effective treatment to fight cancer. However, it not only affects cancer cells but also healthy tissues, causing side effects. Different factors can influence the appearance of radiotoxicity, like total dose administered or patient individual characteristics, such as genetic variability. Several biomarkers have been proposed to predict radiotoxicity, especially those based on apoptosis or DNA damage, for example {gamma}-H2AX, which correlates with DNA double strand breaks. Our purpose is to analyze how apoptosis and {gamma}-H2AX correlate to each other and to link these results with selected SNPs associated with apoptosis. Blood samples from 60 breast cancer patients in remission were recruited. After mononucleated cells isolation, samples were irradiated. Then, we assessed induction and kinetics of disappearance of {gamma}-H2AX at different times after 2-Gy irradiation and apoptosis induced 24 and 48 h after 8-Gy irradiation. A negative correlation was observed between basal and residual {gamma}-H2AX and apoptosis at 48 h post-irradiation. This result supports previous studies with cancer patients showing a negative correlation between these two biomarkers. Considering the high variability of radio-induced apoptosis, we performed a genotyping study. Two SNPs located at TP53 and FAS genes were associated with apoptosis. Overall, our results indicate that individuals with less efficiency in removing damaged cells, probably due to genetic polymorphisms, presented more basal and residual levels of DNA damage.