Radiation-induced up-regulation of telomerase in KG1a cells is influenced by dose-rate and radiation quality.
OBJECTIVE
To examine the influence of dose, dose-rate and radiation quality on telomerase activity (TA) in the KG1a hematopoietic cell line.


METHODS
KG1a cells were irradiated with gamma-rays (0.5-5 Gy) at 0.025 Gy/min, 0.30 Gy/min and 1.57 Gy/min and with a neutron/gamma-ray field (5 Gy). Cell viability was determined by trypan blue exclusion. Apoptosis and cell cycle distribution were evaluated by flow cytometry. Proliferative capacity was studied by MTS assay and TA by PCR. Following 3Gy gamma-irradiation, the expression of hTERT, hTR and TP1 genes was evaluated by RT-PCR.


RESULTS
Dose- and dose-rate-dependent telomerase activation with an increase in hTERT mRNA and a drop in hTP1 mRNA were observed after irradiation. Down-regulation of telomerase activity occurred in a dose-dependent manner. Although non-significant changes in short-term survival were observed after irradiation, late apoptosis became evident after G2/M arrest. Early repression of TA preceded telomerase activation in samples irradiated with a neutron/gamma-ray field, in which short-term survival was affected.


CONCLUSIONS
Radiation-induced telomerase activation depends on dose-rate. High-LET and low-LET irradiations induce similar changes in TA that differ mainly in their kinetics and their magnitude. Changes in TA are not related to cell-cycle redistribution nor to the induction of cell death; they are the consequence of specific regulatory responses to ionizing radiation. Mechanisms including both transcriptional and post-translational control may be involved in this regulation.
Pérez
M del Rosario
Mdel R
Autoridad Regulatoria Nuclear, Gerencia de Apoyo Científico, Laboratorio de Radiopatología, Av del Libertador 8250, CP 1429 Buenos Aires, Argentina.
Dubner
D
D
Michelin
S
S
Leteurtre
F
F
Carosella
E D
ED
Gisone
P A
PA
D017209:Apoptosis; D002453:Cell Cycle / Q000528:radiation effects; D002470:Cell Survival; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D006801:Humans; D007700:Kinetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism / Q000528:radiation effects*; D019098:Telomerase / Q000096:biosynthesis* / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D015854:Up-Regulation
D012333:RNA, Messenger; D019098:Telomerase