Abstract
Cellular radiosensitivity is directly correlated with the mechanism of DNA repair, in which p53 protein plays a major role. In this context, this study correlated cell death with p53 expression in lymphocytes irradiated in vitro with different doses of gammaradiation. For this, peripheral blood samples were collected from 10 healthy subjects. Each sample was divided in aliquots and, separately, irradiated with doses of 0,5; 2 and 4 Gy. After this, peripheral blood mononuclear cells (PBMCs) were isolated and cultivated during 72 hours in 5% CO2 at 37oC without mitogen stimulation. The expression of p53 protein was evaluated by flow cytometry. In parallel, cell viability was determined by trypan blue staining. Statistical analysis was performed us-ing analysis of variance (ANOVA), differences were considered as statistically significant when p < 0.05. The results showed an increase of p53 expression with the absorbed dose, which was proportional to cell death, suggesting that p53 can be used as bioindicator of individual radiosensitivity.
Highlights
About 50% of all cancer patients in the World undergo radiotherapy at some point of their treatment, being 60% of them treated with curative intent [1]
A decrease in cell viability was found in irradiated cells after 72 hours of culture, and it was directly proportional to the absorbed dose
The decline in peripheral blood mononuclear cells (PBMCs) viability after irradiation occurred probably due to cell death by apoptosis, as the latter is the dominant mode of radiation-induced cell-killing mechanism in human lymphocytes [18,19], we did not investigate apoptosis in this study
Summary
About 50% of all cancer patients in the World undergo radiotherapy at some point of their treatment, being 60% of them treated with curative intent [1]. The invasive characteristic of cancer implies that target volume to be irradiated is generally outlined beyond the tumor boundaries, which leads to side effects of radiotherapy that are caused by damage of normal tissues. Post-irradiation side effects occur as a function of individual radiosensitivity, which is correlated with genetically determined intrinsic differences in the cellular and molecular response to the radio induced damage [4,5,6]. This feature was firstly emphasized from patients with rare genetic syndromes, related to mutations in genes involved in the detection and repair of DNA damage [7]
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