Reduction of telomeric signals in murine melanoma and human breast cancer cell lines treated with 3'-azido-2'-3'-dideoxythymidine.
The purpose of this study was to determine, using fluorescence in situ hybridization (FISH), whether treatment of cancer cells with 3'-azido-2'-3'-dideoxythymidine (AZT) has any effect on telomere length as determined by the telomeric signal intensity. To do so, we treated a metastatic murine melanoma cell line (K-1735 clone X-21) and a human breast cancer cell line (MCF-7) with three concentrations of AZT for 72 h at 37ûC. FISH preparations processed using an all-human telomeric DNA probe showed a significantly reduced, concentration-dependent telomeric signal intensity in interphase and metaphase spreads of AZT-treated cells as compared with the signal intensity in untreated controls, which showed no reduction. We conclude from these preliminary results that AZT has the potential of targeting the telomeric ends of chromosomes in cancer cells and promoting cell death and could well be tested along with other chemotherapy drugs given to cancer patients for this purpose.
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
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D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D008545:Melanoma / Q000201:enzymology / Q000235:genetics*; D008677:Metaphase; D051379:Mice; D019098:Telomerase / Q000037:antagonists & inhibitors; D016615:Telomere / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D015215:Zidovudine / Q000031:analogs & derivatives / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D015215:Zidovudine; D019098:Telomerase