Long but dysfunctional telomeres correlate with chromosomal radiosensitivity in a mouse AML cell line

Purpose : To compare the chromosomal radiosensitivity of C3H mouse acute my eloid leukaemia (AML) cell lines 7926 and 8709 and to investigate the mecha nistic basis of the radiosensitivity observed in 7926. Materials and methods : Yields of chromosome aberrations following X-irradi ation were determined in Giemsa-stained metaphases. Cell cycle phase distri butions were determined by BrdU incorporation and microscopy, apoptosis was assessed by caspase assays. Telomerase activity (TRAP assay), telomere len gth (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 3-24 h after 0.5 and 1 Gy X-ray expo sure. This difference could not be accounted for by differences in chromati d break-rejoining rates, cell cycle phase distribution or the induction of apoptosis. Telomeres and telomerase were dysfunctional in 7926. However, av erage telomere length was approximately two-fold greater than in 8709. Conclusion : Defective telomere function in 7926 correlates with chromosoma l radiosensitivity. This implicates telomere function in addition to telome re length as a determinant of chromosomal radiosensitivity.