Effect of chemotherapeutic drugs on telomere length and telomerase activity

Telomeres are specialized nucleoproteic complexes localized at the ends of eukaryotic chromosomes, that maintain their stability and integrity. They protect chromosome ends from fusion and from being recognized as sites of DNA damage, i.e., they distinguish natural DNA ends from DNA ends resulting from breakage events. In mammalian cells, telomeres consist of tandem arrays of the hexanucleotide TTAGGG, oriented 5′ to 3′ towards the end of the chromosomes and associated proteins (the so-called “shelterin” complex), and a large non-coding RNA (named TERRA) which forms an integral component of telomeric heterochromatin. Telomere length is maintained by a dynamic process of telomere shortening and lengthening. Shortening can occur due to nucleolytic degradation and incomplete DNA replication due to the inability of lagging strand synthesis to completely replicate chromosomal ends (i.e., the “end replication problem”), whereas lengthening is primarily accomplished by the action of the enzyme telomerase and occasionally by the so-called Alternative Lengthening of Telomeres (“ALT”) mechanism, which involves homologous recombination. The maintenance of telomere function is crucial for genomic stability and cell viability. Cells respond to dysfunctional telomeres by undergoing senescence, cell death, or genomic instability. Since telomeres play a fundamental role in maintaining chromosomal/genomic stability and telomerase activity and telomere lengthening play a key role in cancer development and progression, a proper knowledge of the effects of chemotherapeutic drugs on telomere length and telomerase activity in normal as well as tumor cells is of great importance to understand the genomic instability associated with chemotherapy regimens. Therefore, in this review we will summarize our current knowledge concerning the main data available about the effects of chemotherapeutic drugs on telomere length and telomerase activity in mammalian cells.Instituto Multidisciplinario de Biología Celula

Telomere Instability Induced by Anticancer Drugs in Mammalian Cells

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 DNA double-strand break. At 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. At the molecular level, telomere instability arises due to the loss or modification of any of the components of the telomere (telomere DNA, telomere-associated proteins or telomere RNA). 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

Effect of chemotherapeutic drugs on telomere length and telomerase activity

Telomeres are specialized nucleoproteic complexes localized at the ends of eukaryotic chromosomes, that maintain their stability and integrity. They protect chromosome ends from fusion and from being recognized as sites of DNA damage, i.e., they distinguish natural DNA ends from DNA ends resulting from breakage events. In mammalian cells, telomeres consist of tandem arrays of the hexanucleotide TTAGGG, oriented 5′ to 3′ towards the end of the chromosomes and associated proteins (the so-called “shelterin” complex), and a large non-coding RNA (named TERRA) which forms an integral component of telomeric heterochromatin. Telomere length is maintained by a dynamic process of telomere shortening and lengthening. Shortening can occur due to nucleolytic degradation and incomplete DNA replication due to the inability of lagging strand synthesis to completely replicate chromosomal ends (i.e., the “end replication problem”), whereas lengthening is primarily accomplished by the action of the enzyme telomerase and occasionally by the so-called Alternative Lengthening of Telomeres (“ALT”) mechanism, which involves homologous recombination. The maintenance of telomere function is crucial for genomic stability and cell viability. Cells respond to dysfunctional telomeres by undergoing senescence, cell death, or genomic instability. Since telomeres play a fundamental role in maintaining chromosomal/genomic stability and telomerase activity and telomere lengthening play a key role in cancer development and progression, a proper knowledge of the effects of chemotherapeutic drugs on telomere length and telomerase activity in normal as well as tumor cells is of great importance to understand the genomic instability associated with chemotherapy regimens. Therefore, in this review we will summarize our current knowledge concerning the main data available about the effects of chemotherapeutic drugs on telomere length and telomerase activity in mammalian cells.Instituto Multidisciplinario de Biología Celula

Chromosomal aberrations involving telomeres and interstitial telomeric sequences

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.Instituto Multidisciplinario de Biología CelularFacultad de Ciencias Naturales y Muse

The role of anions in the electrochemical behaviour of thick palladium oxide layers : Effect of chloride ions

The Influence of chloride ions on the elec trochemical hehaviour of palladium oxide films grown at 2.00 V in 1 M H2SO4 + x M HCl (0 < x < 10-5) is investigated by means of voitamilletry. rotating ring-disk and potential step techniques. Both volltammetric and current transients electro reduction data show that the presence of Cl- ions accelerate the electroreduction of palladium oxide films. The potential of the (Electroreduction voltammetric peak increases with the chloride concentration. Cathodic current transients show current maxima related to the presence of a nucleation and growth process. The mechanism of palladium oxide layer electroreduction can be interpreted through the formation of chloride containing complex species which favours the electroreduction by decreasing the time needed to start the nucleation and growth of the new electroreduced phase. This effect is achieved by the breakdown of the anodic layer. The results are discussed within the frame of da ta previously obtained for perchlorale, phosphate and sulphate ion-containing solution.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Evolución y creación

No existe necesariamente contradicción entre los conceptos de “creación” y de “evolución”: el primero se refiere al origen absoluto de las cosas mientras que el segundo intenta explicar la formación y desarrollo de esos entes originales hasta dar lugar a la aparición de entes vivientes y sus transformaciones con el correr del tiempo. Por ahora me dedicaré especialmente al concepto filosófico de “creación” a fin de comprender el origen absoluto de los seres naturales y el acto mismo de creación. Crear no es un proceso de hacer cosas sino el acto de hacer que las cosas sean, teniendo el ser creado su consistencia en ser-creado, dependiendo esencialmente de su relación al creador y existiendo precisamente en esta relación. En este sentido “creación” es la más singular de las singularidades y no puede ser objeto de la ciencia puesto que el objetivo de la ciencia es comprender tan completamente como sea posible el sistema existente de los seres y sus cambios, ya se trate del Big Bang, de la evolución biológica o de cualquier otro campo del saber teórico-experimental.The concepts “creation” and “evolution” are not necessarily contradictories: the first refers to the absolute origin of things, while the second one attempts to explain the formation and development of those original beings into living beings and their transformations through time. This lecture will particularly deal with the philosophical concept of “creation” in order to understand the absolute origin of natural beings and the very act of creation. Creation is not a process to make things but an act to cause things to be, by which the created being gets consistence in the act of being created, depending absolutely upon its relationship with the creator and just existing in this relationship. In this sense creation is the most singular of singularities and cannot be subject of science because the aim of science is to understand as completely as possible the system of already existing beings and its mutations as far as every process happens inside a given system of beings, either by the Big Bang, the biological evolution, or any other field of experimental and theoretical knowledge.Facultad de Ciencias Naturales y Muse

Estudio de la reacción de disociación ácida (hidrólisis) de ión ferroso en el perclorato ferroso

El objeto de nuestro estudio ha sido la reacción de diso-ciación ácida (hidrólisis) del ión ferroso en la forma de perclorato ferroso. La información que hemos podido recoger sobre este tema es escasa. Sólo hemos hallado los trabajos de Lindstrund y de Hedstrom donde se han medido valores de la constante de disocíación, y el de Leussing y Kolthoff, quienes han calculado la constante en base a medidas de la solubilidad del hidróxído ferroso; en los tres casos mencionados las mediciones se hicieron a una única temperatura y los datos aportados son discordantes. Las investigaciones precitadas difieren notablemente en los valores hallados para el pK de la hidrólisis del ión ferroso y esa diferencia es tan grande que tampoco puede justificarse por el hecho de que todos estos autores hayan usado distintos métodos de medida. Por otra parte en ninguno de estos trabajos se ha intentado verificar la dependencia de los valores del pK con la temperatura, lo que hubiera sido importante porque habría servido de esclarecimiento frente a una discrepancia tan seria como la recientemente señalada. Por esta razón hemos creído de interés realizar este trabajo sobre la hidrólisis del ión ferroso pues, entre otros, esta reacción juega un papel importante en los procesos de corrosión en los cuales interviene este metal. También el conocimiento de la dependencia de la constante de hidrólisis con la temperatura permite hallar algunas magnitudes termodinámicas de importancia vinculadas a ella.Tesis digitalizada en SEDICI gracias a la Biblioteca Central de la Facultad de Ciencias Exactas (UNLP).Al momento de presentación de esta tesis, la actual Facultad de Ciencias Exactas se denominaba Facultad de Química y Farmacia.Facultad de Ciencias Exacta

Fast faradaic processes observed during the potentiodynamic polarization of polycrystalline palladium in acid electrolyte

Two almost reversible electrochemical systems are detected during the potentiodynamic anodization of polycrystalline palladium in 1 M H2SO4 and 1 M HClO4 by applying the triangular modulated triangular potential sweep technique. The first electrochemical system which appears in the 0.7–0.9 V range (vs. RHE) corresponds to the reaction Pd+H2O=PdOH+H++e− whose reversible potential is estimated as 0.80±0.02 V and the average half-life time of PdOH species is estimated as 6×10−3 s. The second electrochemical system appears when the anodizing potential sweep extends to the oxygen evolution potential region. The appearance of the second electrochemical system is accompanied by a change in colour of the electrode surface, a shift of the current-potential curve of the oxygen evolution reaction and an increase in thickness of the oxide anodic layer. The reversible response is tentatively assigned to the PdO2/PdO3 redox couple.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasFacultad de Ciencias Exacta

Fast faradaic processes observed during the potentiodynamic polarization of polycrystalline palladium in acid electrolyte

Two almost reversible electrochemical systems are detected during the potentiodynamic anodization of polycrystalline palladium in 1 M H2SO4 and 1 M HClO4 by applying the triangular modulated triangular potential sweep technique. The first electrochemical system which appears in the 0.7–0.9 V range (vs. RHE) corresponds to the reaction Pd+H2O=PdOH+H++e− whose reversible potential is estimated as 0.80±0.02 V and the average half-life time of PdOH species is estimated as 6×10−3 s. The second electrochemical system appears when the anodizing potential sweep extends to the oxygen evolution potential region. The appearance of the second electrochemical system is accompanied by a change in colour of the electrode surface, a shift of the current-potential curve of the oxygen evolution reaction and an increase in thickness of the oxide anodic layer. The reversible response is tentatively assigned to the PdO2/PdO3 redox couple.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasFacultad de Ciencias Exacta

The electrodissolution of base palladium in relation to the oxygen electroadsorption and electrodesorption in sulphuric acid solution

The electrodissolution of palladium electrode immersed in 1 M H2SO4 under both repetitive triangular potential sweeps and combined potential perturbation functions has been investigated by using the rotating ring—disc electrode technique. The contribution of palladium electrodissolution in the voltammogram changes in going from the first potential scan to the following ones. This contribution also depends on the characteristics of the potential perturbation programme applied to the electrode. Different potential ranges associated with the formation of soluble palladium(II) are distinguished, which correlate with those corresponding to electrochemical reactions already established. The results are explained through a competitive reaction pathway involving the formation of Pd(OH) and Pd(OH)+ intermediate species. The influence of ageing effects and anion adsorption on the formation of soluble palladium(II) is also discussed.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasFacultad de Ciencias Exacta