Are telomeres a specific target for mutagenic attack by cytostatics in neoplastic cells?
Damage to telomeres induced by cytostatic therapy theoretically could generate telomere shortening and, subsequently, induce an additional genomic instability in neoplastic cells. Model experiments were carried out to examine this hypothesis. Cells of the T-ALL derived cell line CCRF-CEM were exposed to various different concentrations of Bleomycin (BLM) or Mitomycin C (MMC) for various times. Telomere lengths of metaphase chromosomes of the exposed cells were compared with those without this exposure (controls). In addition, telomerase activity was determined with a TRAP assay under the given conditions using the BLM experiments as a model. Although slight changes of total telomere length could be found in single experiments, the differences between exposed and non-exposed cells were not significant. Also, a considerable telomerase activity was shown which, however, did not substantially differ between exposed and non-exposed cells. From these data it may be concluded that, at least in the examined cell line, telomeres are not a preferential target for this kind of mutagenic attack.
Wick
U
U
Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
Gebhart
E
E
D001761:Bleomycin / Q000633:toxicity; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004249:DNA Damage; D006801:Humans; D016685:Mitomycin / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016615:Telomere / Q000187:drug effects*
D009153:Mutagens; D001761:Bleomycin; D016685:Mitomycin; D019098:Telomerase