Alterration of telemere repeated seauences in immortal human cells and their nuclear chromosomal localization.

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Immortalization of human cells is often associated with reactivation of telomerase, a ribonucleoprotein enzyme that add TTAGGG repeats onto telomeres and compensates for their shortening. We examined whether telomerase activation is necessry for immortalization by SV40 infection or 60-Co irradiation. Three human embryonal fibroblast transformants (SW38sv, IMR90sv, KMST-6) revealed distinct elongation of telomere repeated sequene inspite of the absence of telomerase activity in these cells. These observations suggest that activation of telomerase gene is not sufficient for immortalization of human fibroblasts. Fluorescence in situ hybridization (FISH), using telomere repeats repeats as a probe represents the regional amplification of telomere repeats in the nucleus. These amplified telomere sequences were also mapped to the end of a few chromosomes revealing that the elongation of telomere repeats was the results of regional amplification of telomere repeats. Taken together, these data suggest that the transormed cell gains stabilized telomere by a novel and as yet unidentified mechanism without telomerase gene activation.