Long but dysfunctional telomeres correlate with chromosomal radiosensitivity in a mouse AML cell line.
OBJECTIVE
To compare the chromosomal radiosensitivity of C3H mouse acute myeloid leukaemia (AML) cell lines 7926 and 8709 and to investigate the mechanistic basis of the radiosensitivity observed in 7926.


METHODS
Yields of chromosome aberrations following X-irradiation were determined in Giemsa-stained metaphases. Cell cycle phase distributions were determined by BrdU incorporation and microscopy, apoptosis was assessed by caspase assays. Telomerase activity (TRAP assay), telomere length (Q-FISH and Southern blotting) and telomere function (Robertsonian-like fusion formation) were also examined. The expression levels of telomerase components, telomerase regulators and DNA PKcs were determined on Northern blots.


RESULTS
A total of 4.5-7.6-fold elevated chromosome aberration yields were found in 7926 by comparison with 8709 3-24h after 0.5 and 1 Gy X-ray exposure. This difference could not be accounted for by differences in chromatid break-rejoining rates, cell cycle phase distribution or the induction of apoptosis. Telomeres and telomerase were dysfunctional in 7926. However, average telomere length was approximately two-fold greater than in 8709.


CONCLUSIONS
Defective telomere function in 7926 correlates with chromosomal radiosensitivity. This implicates telomere function in addition to telomere length as a determinant of chromosomal radiosensitivity.
Finnon
P
P
National Radiological Protection Board, Chilton, Didcot X11 ORQ, UK. paul.finnon@nrpb.org.uk
Wong
H P
HP
Silver
A R
AR
Slijepcevic
P
P
Bouffler
S D
SD
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015139:Blotting, Southern; D002875:Chromosomes / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004587:Electrophoresis, Agar Gel; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000532:radiotherapy*; D008677:Metaphase; D051379:Mice; D008809:Mice, Inbred C3H; D008938:Mitosis; D009841:Oligonucleotides / Q000494:pharmacology; D010641:Phenotype; D011836:Radiation Tolerance; D016196:S Phase; D017422:Sequence Analysis, DNA; D019098:Telomerase / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014965:X-Rays
D009841:Oligonucleotides; D019098:Telomerase