Relazione tra danno primario al DNA, riparazione e danno cromosomico: implicazioni terapeutiche
Author(s)
Mancinelli, Pierluigi
Date Issued
October 3, 2008
Type
Doctoral Thesis
Abstract
To learn more about the biological effects of radiations, we examined radiation-induced apoptosis in response to x-ray irradiations in human peripheral blood lymphocytes (HPBL). HPBL were exposed to x-rays in the presence or absence of Pifithrin-α (PFT-α), a transcriptional trans-activation reversible inhibitor for p53 protein, both in the G0 and in the G2 phase of cell cycle. Experiments with HPBL in the G2 phase demonstrate that PFT-α does not affect cell cycle kinetics both in irradiated cells and in control samples and indicate the existence of a p53-independent apoptotic pathway in human lymphocytes in this phase of the cell cycle. Alkaline Comet-assay was performed at early recovery times (0h to 4h) after irradiation in the G0 phase, to test HPBL DNA repair capability in the presence or absence of PFT-α after irradiation. A delayed repair kinetic was observed in lymphocytes co-treated with x-rays and PFT-α respect to only x-ray-irradiated lymphocytes. The parallel analysis of both nuclear morphology and chromosomal aberrations indicated a time-dependent correlation between decrease in the yield of apoptotic cells and increase in the frequency of both dicentrics and aberrant cells. The overall data demonstrate that the inhibition of p53-mediated apoptosis promotes the enhancement of chromosomal aberrations in G0 x-ray-irradiated HPBL. PFT-α then, beside its direct effect on apoptosis could have an effect also on DNA repair processes increasing the mis-repair of X-rays-induced chromosomal damage.
Additional information
Dottorato di ricerca in Evoluzione biologica e biochimica
Subjects
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