Genetic instability and telomere shortening in normal human fibroblasts after irradiation with X-rays

Introduction Former experiments have shown an increased number of non-transmissible chromosomal aberrations in the progeny of normal human fibroblasts after irradiation with Xrays [1, 2]. These de novo formed non-transmissible aberrations are an indicator of genomic instability which is considered to be one important step towards carcinogenesis. In parallel experiments we observed accelerated shortening of telomeres in the descendants of normal human fibroblasts [3]. Telomere shortening and dysfunction is believed to play an important role in promoting genomic instability by forming end-to-end fusions of chromosomes and giving rise to further breakage-fusionbridge cycles. Telomeric fusions are rarely found in normal proliferating cells but frequently observed in virus infected, tumor or senescent cells. This mechanism is, among others, responsible for gene amplification, a phenomenon relevant for carcinogenesis and tumor progression [4].