The influence of interstitial telomeric sequences on chromosome instability in human cells

Although most telomere repeat: sequences are found at the ends of chromosom es, some telomeric repeat sequences are also found at intrachromosomal loca tions in mammalian cells. Several studies have found that these interstitia l telomeric repeat sequences can promote chromosome instability in rodent c ells, either spontaneously or following ionizing radiation. In the present study we describe the extensive cytogenetic analysis of three different hum an cell lines with plasmids containing telomeric repeat sequences integrate d at: interstitial sites. In two of these cell lines, Q18 and P8SX, instabi lity has been detected in the chromosome containing the integrated plasmid, involving breakage/fusion/bridge cycles or amplification of the plasmid DN A, respectively. However, the data suggest that the instability observed is characteristic of the general instability in these cell lines and that the telomeric repeat sequences themselves are not responsible. Consistent with this interpretation, the chromosome containing an integrated plasmid with 500 bp of telomeric repeat sequences is highly stable in the third cell lin e, SNG28, which has a relatively stable genome. The stability of the chromo some containing the integrated plasmid sequences in SNG28 makes this an exc ellent cell line to study the effect of ionizing radiation on the stability of interstitial telomeric sequences in human cells.