IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
artículos
Título:
Telomere instability is present in the progeny of mammalian cells exposed to bleomycin
Autor/es:
PAVIOLO, N.S.; QUIROGA, I.Y.; CASTROGIOVANNI, D.C.; BIANCHI, M.S.; BOLZÁN, A.D.
Revista:
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2012 vol. 734 p. 5 - 11
ISSN:
0027-5107
Resumen:
We analyzed the chromosomal aberrations involving telomeres in the
progeny of mammalian cells exposed to the radiomimetic compound bleomycin (BLM)
in order to determine if this antineoplastic drug induces long-term telomere
instability. To this end, rat cells (ADIPO-P2 cell line, derived from adipose cells
from Sprague-Dawley rat) were treated with a single concentration of BLM (2.5 µg/ml),
and chromosomal aberrations were analyzed 18 h and 10 days after treatment by
using PNA-FISH with a pantelomeric probe [(TTAGGG)n repeats]. Cytogenetic
analysis revealed a higher frequency of aberrations at 18 h and 10 days after
treatment in BLM-exposed cultures vs. untreated cultures, although the yield of
BLM-induced aberrations 10 days after treatment decreased about 25% compared
with the one at 18 h after treatment. Moreover, the level of telomerase
activity in BLM-treated cells compared with that of untreated control cells was significantly higher at 10 days after treatment,
but did not differ at 18 h after treatment. These data indicate that in terms
of unstable aberrations, the in vitro clastogenic effect of BLM on ADIPO-P2
cells persists for at least 10 days after exposure. In addition, our data
demonstrate, for the first time, that BLM-induced telomere instability in
mammalian cells (cytogenetically detectable as incomplete chromosome elements
and telomere FISH signal loss and duplication) persists for several generations
after exposure. Moreover, the appearance of telomere fusions in BLM-exposed
cells 10 days after treatment suggests that this compound can induce delayed
telomere instability. The increase in telomerase activity in BLM-exposed cells
10 days after treatment is accompanied by the presence of aberrations directly
related to telomere dysfunction. This fact suggests that telomerase is not
directly involved in BLM-induced telomere instability.