X-irradiated human lymphocytes with unstable aberrations and their preferential elimination by p53/survivin-dependent apoptosis.
OBJECTIVE
To investigate whether unstable types of chromosomal aberrations are more effective in priming apoptotic cell death in comparison with stable ones. Also, to highlight the phase of the cell cycle at which apoptosis occurs and the mechanism of its execution.


METHODS
G0 human peripheral blood lymphocytes were X-irradiated in the presence or absence of the repair inhibitor cytosine arabinoside (Ara-C). After irradiation, the lymphocytes were analysed for induction of dicentrics, translocations, apoptosis, p53 and survivin expression at various recovery times.


RESULTS
A preferential elimination of cells bearing dicentrics with respect to those with balanced translocations was observed. There was a time-dependent correlation between the decrease in the frequency of dicentrics and the increase in the per cent of apoptotic cells. Most of the apoptotic cells were labelled with bromodeoxyuridine and were mononucleated in cytochalasin B-treated cells cultures (blocked cytokinesis). However, after continuous colcemid treatment, the apoptotic pathway was not induced. Moreover, in the G2/M-phase, an increase in p53 and a decrease in survivin occurred that were X-ray and Ara-C dose dependent.


CONCLUSIONS
The apoptotic process is primed when the dicentric-bearing human peripheral blood lymphocytes attempt to exit from metaphase. It is possible that unstable aberrations generate changes in the mitotic spindle causing mechanical tension at the kinetochore, activating the mitotic checkpoint and the execution of p53/survivin-dependent apoptosis.
Bassi
L
L
Dipartimento di Agrobiologia e Agrochimica, Università degli Studi della Tuscia, Via San Camillo De Lellis, I-01100, Viterbo, Italy..
Carloni
M
M
Meschini
R
R
Fonti
E
E
Palitti
F
F
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000145:classification* / Q000528:radiation effects*; D002877:Chromosomes, Human / Q000145:classification / Q000528:radiation effects; D003561:Cytarabine / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins; D011829:Radiation Dosage; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014965:X-Rays
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D003561:Cytarabine