Bleomycin-induced chromosomal aberrations in Epstein-Barr virus-transformed human lymphoblastoid cells

Abstract

We have evaluated the induction of complete (i.e., without open ends) and incomplete (i.e., with non-rejoined oropen ends) chromosomal aberrations by the radiomimetic antibiotic bleomycin (BLM) in human lymphoblastoidcells immortalized with the Epstein-Barr virus (EBV). An EBV-induced lymphoblastoid cell line (T-37) wasexposed to BLM (10–200 µg/mL) for 2 h at 37ºC, and chromosomal aberrations were analyzed 24 h aftertreatment, using PNA-FISH with pan-telomeric and pan-centromeric probes. Both complete (multicentrics, rings,compound acentric fragments, and interstitial deletions) and incomplete (incomplete chromosomes or IC, andterminal acentric fragments or TAF) chromosomal aberrations increased significantly in BLM-exposed cells,although the concentration-response relationship was non-linear. Of the acentric fragments (ace) induced byBLM, 40 % were compound fragments (CF, ace +/+). TAF (ace, +/-) and interstitial fragments (IAF, ace -/-) wereinduced at similar frequencies (30 %). 230 ICE were induced by BLM, of which 52 % were IC and 48 % TAF. Theaverage ratio between total incomplete chromosome elements (ICE) and multicentrics was 1.52. These findingssuggest that human lymphoblastoid cells exhibit less repair capacity than human lymphocytes, with respect toBLM-induced ICE, and that chromosomal incompleteness is a common event following exposure of these cells toBLM.