The antineoplastic agent streptozotocin induces short-term telomere instability in Epstein-Barr virus-transformed human lymphoblastoid cells

Abstract

We assessed the induction of telomere instability-related chromosomal aberrations by streptozotocin (STZ) inhuman lymphoblastoid cells (T-37) immortalized with Epstein-Barr virus (EBV) using Peptide Nucleic Acid-Fluorescence In Situ Hibridization (PNA-FISH) with pan-telomeric and pan-centromeric probes. Cells wereexposed to STZ at concentrations ranging from 0.5 to 4.0 mM in sodium citrate (SC, pH 4.4) for 1 h at 37 ◦C, andchromosomal aberrations were analyzed 24 h later. Incomplete chromosome elements (ICE) significantly increasedafter STZ treatments at 2 and 4 mM compared to untreated and SC-treated cultures (p <0.05). The total number oftelomeric signals lost (TSL) and the frequency of chromosome-type telomere signal loss per cell rose significantlyafter STZ treatments of 0.5 and 1 mM compared to untreated and SC-treated cultures (p <0.05). Both SC and STZcaused chromatid-type telomere signal loss and duplications (TSD), but differences between these treatments werenon-significant (p >0.05). Non-significant differences between treatments in terms of telomere fusions, associations,ectopic signals, or sister-chromatid telomere fusions were observed (p >0.05). Quantitative FISH (Q-FISH)revealed longer telomeres in cells treated with SC (10 and 60 μL) or STZ (0.5, 1, and 3 mM) compared to untreatedcells (p <0.05), with non-significant differences between SC and STZ (p >0.05). These results indicate that STZinduces short-term telomere instability, while suggest that SC induces telomere dysfunction and elongation inhuman lymphoblastoid cells.