TELOMERES AND RADIATION-INDUCED CHROMOSOME BREAKAGE

Molecular characterization of some cytologically apparent terminal del etions in human tumours revealed that these were subtelomeric cryptic translocations undetectable by classical cytogenetic methods, To deter mine whether subtelomeric cryptic translocations occur following expos ure of mammalian cells to ionizing radiation we used four cell lines e xhibiting variable telomere lengths, Our G(1) and G(2) radiation exper iments revealed that a small percentage of broken chromosomes exhibite d telomeric signals, This occurred exclusively in cell lines exhibitin g FISH-detectable telomeres, suggesting that telomeric signals at radi ation-induced chromosome breaks were the result of subtelomeric crypti c translocations. In addition, telomeric signals at G(2) chromatid bre aks were usually paired with telomeres of intact sister chromatids, fu rther supporting the notion that subtelomeric cryptic translocations a re responsible for the presence of telomeric sequences at radiation-in duced chromosome breaks. In one of the cell lines we identified what l ooked like de novo telomeric signals at derived chromatid breaks obser ved 20 h following irradiation, Our previous study suggested that thes e signals may be the result of amplification of interstitial telomeric sites in the first cell cycle and spontaneous breakage of interstitia l telomeric sites in subsequent cell cycles, Taken together our result s suggest that a small percentage of radiation-induced chromosome/chro matid breaks may be modified by subtelomeric cryptic translocations an d that interstitial telomeric sites may be involved in radiation-induc ed chromosome instability.