Telomeres and radiation-induced chromosome breakage.

Abstract

Molecular characterization of some cytologically apparent terminal deletions in human tumours revealed that these were subtelomeric cryptic translocations undetectable by classical cytogenetic methods. To determine whether subtelomeric cryptic translocations occur following exposure of mammalian cells to ionizing radiation we used four cell lines exhibiting variable telomere lengths. Our G1 and G2 radiation experiments revealed that a small percentage of broken chromosomes exhibited telomeric signals. This occurred exclusively in cell lines exhibiting FISH-detectable telomeres, suggesting that telomeric signals at radiation-induced chromosome breaks were the result of subtelomeric cryptic translocations. In addition, telomeric signals at G2 chromatid breaks were usually paired with telomeres of intact sister chromatids, further supporting the notion that subtelomeric cryptic translocations are responsible for the presence of telomeric sequences at radiation-induced chromosome breaks. In one of the cell lines we identified what looked like de novo telomeric signals at derived chromatid breaks observed 20 h following irradiation. Our previous study suggested that these signals may be the result of amplification of interstitial telomeric sites in the first cell cycle and spontaneous breakage of interstitial telomeric sites in subsequent cell cycles. Taken together our results suggest that a small percentage of radiation-induced chromosome/chromatid breaks may be modified by subtelomeric cryptic translocations and that interstitial telomeric sites may be involved in radiation-induced chromosome instability.