A comparative analysis of bleomycin‐induced incomplete chromosome elements in two mammalian cell lines using a telomeric PNA probe

Flaqué, María Celeste Díaz; Bianchi, Martha S.; Bolzán, Alejandro D.

doi:10.1002/em.20254

Cited by 12 publications

(9 citation statements)

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“…1A). On the other hand, the high spontaneous frequency of IC and acentric fragments observed in control cells (Table 1a) cannot be linked to the results of the FISH analysis and is similar to that found in other mammalian cell lines, previously investigated in our laboratory for telomere instability [17,[30][31][32]. Furthermore, the significant increase in the frequency of telomere FISH signal loss found in control cells 10 and 15 days after treatment (Table 1b) could be due to spontaneous extensive telomere shortening, a phenomenon usually observed in in vitro cultured cells [1][2][3][4].…”

Section: Chromosome Damage and Distribution Pattern Of Telomeric Sequsupporting

confidence: 76%

The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells

Paviolo

Santiñaque

Castrogiovanni

et al. 2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

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We analyzed chromosomal aberrations involving telomeres in the progeny of mammalian cells exposed to the methylating agent and antineoplastic/diabetogenic drug streptozotocin (STZ), to test whether it induces long-term telomere instability (by chromosome end loss and/or telomere dysfunction). Rat cells (ADIPO-P2 cell line, derived from Sprague-Dawley rat adipose cells) were treated with a single concentration of STZ (2mM). Chromosomal aberrations were analyzed 18h, 10 days, and 15 days after treatment, using PNA-FISH with a pan-telomeric probe [Cy3-(CCCTAA)3] to detect (TTAGGG)n repeats. Cytogenetic analysis revealed a higher frequency of chromosomal aberrations in STZ-exposed cultures vs. untreated cultures at each time point analyzed. The yield of induced aberrations was very similar at each time point. Induction of aberrations not involving telomere dysfunction was only observed 18h and 15 days after treatment, whereas induction of telomere dysfunction-related aberrations by STZ (mainly in the form of telomere FISH signal loss and duplications, most of them chromatid-type aberrations) was observed at each time point. Our results show that STZ induces persistent telomere instability in mammalian cells, cytogenetically manifested as telomere dysfunction-related chromosomal aberrations. Neither telomere length nor telomerase activity is related to the telomere dysfunction.

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Section: Chromosome Damage and Distribution Pattern Of Telomeric Sequsupporting

confidence: 76%

The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells

Paviolo

Santiñaque

Castrogiovanni

et al. 2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…Chromosomal aberrations involving the chromosome ends or the telomeric sequences located at the chromosome ends Several publications refer to the application of telomere FISH to analyse the induction of ICEs and IFs by low-and high-LET radiations and chemical mutagens (51,(58)(59)(60)(61)89,90,92,(128)(129)(130)(131)(132)(133) [see (1,39) for review]. These studies include the analysis of all types of asymmetrical chromosome aberrations induced by ionising radiation and the radiomimetic compound bleomycin in human lymphocytes and the ones induced by this compound and the antibiotics streptonigrin and streptozotocin in Chinese hamster cells.…”

Section: Induction Of Chromosomal Aberrations Involving Telomeres And...mentioning

confidence: 99%

“…It was found that the main form of ICEs (Figure 2) induced by clastogenic agents-irrespective of their mode of action-consists of pairs ICs þ TFs (Figure 2A, Case 1) (59,(128)(129)(130)(131). The predominance of some form of ICE over the other ones might be explained by the attachment of the telomeres to the nuclear matrix [see (1) for discussion].…”

Section: Induction Of Chromosomal Aberrations Involving Telomeres And...mentioning

confidence: 99%

“…The predominance of some form of ICE over the other ones might be explained by the attachment of the telomeres to the nuclear matrix [see (1) for discussion]. Moreover, all of the studies performed so far show that ICEs are the most frequent type of asymmetrical chromosome aberrations induced by chemical mutagens (128)(129)(130)(131). The only exception was found in bleomycin-exposed human lymphocytes, where dicentric chromosomes predominated over ICEs (90).…”

Section: Induction Of Chromosomal Aberrations Involving Telomeres And...mentioning

confidence: 99%

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Chromosomal aberrations involving telomeres and interstitial telomeric sequences

Bolzán¹

2011

Mutagenesis

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Telomeres are specialised nucleoproteic complexes localised at the physical ends of linear eukaryotic chromosomes that maintain their stability and integrity. In vertebrate chromosomes, the DNA component of telomeres is constituted by (TTAGGG)n repeats, which can be localised at the terminal regions of chromosomes (true telomeres) or at intrachromosomal sites (interstitial telomeric sequences or ITSs, located at the centromeric region or between the centromere and the telomere). In the past two decades, the use of molecular cytogenetic techniques has led to a new spectrum of spontaneous and clastogen-induced chromosomal aberrations being identified, involving telomeres and ITSs. Some aberrations involve the chromosome ends and, indirectly, the telomeric repeats located at the terminal regions of chromosomes (true telomeres). A second type of aberrations directly involves the telomeric sequences located at the chromosome ends. Finally, there is a third class of aberrations that specifically involves the ITSs. The aims of this review are to provide a detailed description of these aberrations and to summarise the available data regarding their induction by physical and chemical mutagens.

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“…The abovementioned studies, perfomed using FISH with a Peptide Nucleic Acid telomere probe (telomere PNA-FISH) in Chinese hamster cells (CHE cell line), showed that all the above drugs can induce the formation of incomplete chromosomes and terminal fragments [55][56][57][58].…”

Section: Bleomycin (Blm) Streptonigrin (Sn) and Streptozotocin (Stz)mentioning

confidence: 99%

Telomere Instability Induced by Anticancer Drugs in Mammalian Cells

Bolzán¹

2016

Telomere - A Complex End of a Chromosome

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Telomere instability results from chromosome end loss due to chromosome breakage at one or both ends or, more frequently, telomere dysfunction. Dysfunctional telomeres arise when they lose their end-capping function or become critically short, which causes chromosomal termini to behave like a DN" double-strand break. "t the chromosomal level, this phenomenon is visualized by using Fluorescence In Situ Hybridization FISH , as chromosomal aberrations directly involving terminal telomeric repeats loss or duplication of telomeric signals, association or fusion of telomeres of different chromosomes, telomere sister chromatid exchanges, translocation or amplification of telomeric sequences, and extrachromosomal telomeric signals. "t the molecular level, telomere instability arises due to the loss or modification of any of the components of the telomere telomere DN", telomere-associated proteins or telomere RN" . Since telomeres play a fundamental role in maintaining genomic stability, the study of telomere instability in cells exposed to anticancer drugs is of great importance to understand the genomic instability associated with chemotherapy regimens. In this chapter, we will summarize our current knowledge about telomere instability induced by anticancer drugs on mammalian cells. Keywords:Telomere, telomere instability, telomere loss, telomere dysfunction, telomere erosion, chemotherapy, anticancer drugs . Introduction . . What are telomeres?Classically defined as the chromosome ends, telomeres from the Greek, telo = end, and mere = part [ ] are nowadays defined as specialized nucleoprotein complexes localized at the physical ends of linear eukaryotic chromosomes, that maintain their stability and integrity [ , ]. They protect chromosomes from degradation, recombination or fusion, by preventing the © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.ends of linear chromosomes from being recognized as DN" double-strand breaks DS" by the DN" repair machinery, i.e., they distinguish natural DN" ends from DN" ends resulting from breakage events [ , ].In all vertebrates, telomeres are composed of tandem arrays of short, repetitive G-rich sequences TT"GGG n, oriented ′ → ′ towards the end of the chromosome, ending in an essential ′ single-stranded overhang that ranges in length from ~ to nt [ -], bound by a specialised multiprotein complex known as shelterin or telosome [ -]. The length of the double-stranded telomeric repeat varies greatly among species [ ]. In normal human cells, the DN" at each chromosome terminus spans -kb in length [ , , ], terminating in a " single-stranded overhang -nt in length [ ], whereas in human tumor cells, telomere length varies from to kb [ -].The telosome is constituted by proteins POT , TPP . TIN , TRF , TRF and R"P and is charged with prot...

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A comparative analysis of bleomycin‐induced incomplete chromosome elements in two mammalian cell lines using a telomeric PNA probe

Cited by 12 publications

References 26 publications

The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells

The methylating agent streptozotocin induces persistent telomere dysfunction in mammalian cells

Chromosomal aberrations involving telomeres and interstitial telomeric sequences

Telomere Instability Induced by Anticancer Drugs in Mammalian Cells

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