Browsing by Author "Martins, C"
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- Effect of poly(ADP-ribosyl)ation inhibitors on the genotoxic effects of the boron neutron capture reactionPublication . Oliveira, NG; Castro, M; Rodrigues, AS; Goncalves, IC; Martins, C; Rico, JMT; Rueff, JThe boron neutron capture (BNC) reaction results from the interaction of B-10 with low-energy thermal neutrons and gives rise to highly damaging lithium and alpha-particles. In this work the genotoxicity caused by the BNC reaction in V79 Chinese hamster cells was evaluated in the presence of poly(ADP-ribosyl)ation inhibitors. Poly(ADP-ribose) polymerase-1 (PARP-1), the most important member of the PARP enzyme family, is considered to be a constitutive factor of the DNA damage surveillance network present in eukaryotic cells, acting through a DNA break sensor function. Inhibition of poly(ADP-ribosyl)ation was achieved with the classical compound 3-aminobenzamide (3-AB), and with two novel and very potent inhibitors, 5-aminoisoquinolinone (5-AIQ) and PJ-34. Dose-response increases in the frequencies of aberrant cells excluding gaps (%ACEG) and chromosomal aberrations excluding gaps per cell (CAEG/cell) were observed for increasing exposures to the BNC reaction. The presence of 3-AB did not increase the %ACEG or CAEG/cell, nor did it change the pattern of the induced chromosomal aberrations. Results with 5-AIQ and PJ-34 were in agreement with the results obtained with 3-AB. We further studied the combined effect of a PARP inhibitor and a DNA-dependent protein kinase (DNA-PK) inhibitors (3-AB and wortmannin, respectively) on the genotoxicity of the BNC reaction, by use of the cytokinesis-block micronucleus assay. DNA-PK is also activated by DNA breaks and binds DNA ends, playing a role of utmost importance in the repair of double-strand breaks. Our results show that the inhibition of poly(ADP-ribosyl)ation does not particularly modify the genotoxicity of the BNC reaction, and that PARP inhibition together with a concomitant inhibition of DNA-PK revealed barely the same sensitizing effect as DNA-PK inhibition per se. (c) 2005 Published by Elsevier B.V.
- Glycidamide-DNA adducts and sister chromatid exchanges in human lymphocytes exposed to acrylamide and glycidamidePublication . Pingarilho, M; Martins, C; Oliveira, NG; Vaz, S; Gamboa da Costa, G; Martins, V; Marques, MM; Beland, FA; Churchwell, MI; Doerge, DR; Rueff, J; Gaspar, JF
- Induction of sister-chromatid exchanges and chromosomal aberrations by acrylamide and glycidamidePublication . Martins, C; Gaspar, J; Martins, V; Gamboa da Costa, G; Marques, MM; Rueff, J; Oliveira, NG
- Intracellular S-adenosylhomocysteine increased levels are associated with DNA hypomethylation in HUVECPublication . Castro, R; Rivera, I; Martins, C; Struys, EA; Jansen, EEW; Clode, N; Graca, LM; Blom, HJ; Jakobs, C; de Almeida, ITHyperhomocysteinemia is a risk factor for atherosclerosis and vascular disease; however, the mechanism underlying this association remains poorly understood. Increased levels of intracellular S-adenosylhomocysteine (AdoHcy), secondary to homocysteine-medi
- Synthesis and Biological Assessment of Furoquinolines, Pyrroloquinolines and Analogues Towards Cholinesterases and Monoamine Oxidases A and BPublication . Martins, C; Carreiras, MC; Mendes, E; de los Rios, C; Léon, R; Ramsay, R; Marco-Contelles, J
- Synthesis, biological evaluation and molecular modelling of diversely functionalized heterocyclic derivatives as inhibitors of acetylcholinesterase/butyrylcholinesterase and modulators of Ca2+ channels and nicotinic receptorsPublication . Marco, JL; de los Rios, C; Garcia, AG; Villarroya, M; Carreiras, MC; Martins, C; Eleuterio, A; Morreale, A; Orozco, M; Luque, FJThe synthesis and the biological activity of compounds 5-40 as inhibitors of acetyleholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as modulators of voltage-dependent Ca2+ channels and nicotinic receptors, are described. These molecules are tacrine analogues, which have been prepared from polyfunctionalized 6-amino-5-cyano-4H-pyrans, 6-amino-5-cyano-pyridines and 5-amino-2-aryl-3-cyano-1,3-oxazoles via Friedlander reaction with selected cycloalkanones. These compounds are moderate acetylcholinesterase and butyrylcholinesterase inhibitors, the BuChE/AChE selectivity of the most active molecules ranges from 10.0 (compound 29) to 76.9 (compound 16). Interestingly, the 'oxazolo-tacrine' derivatives are devoid of any activity. All compounds showed an important inhibitory effect on the nicotinic acetylcholine receptor. Most of them also blocked L-type Ca2+ channels, and three of them, 64, 19 and 67, the non-L type of Ca2+ channels. Molecular modelling studies suggest that these compounds might bind at the peripheral binding site of AChE, which opens the possibility to design inhibitors able to bind at both, the catalytic and peripheral binding sites of the enzyme. (C) 2004 Elsevier Ltd. All rights reserved.