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    ABSTRACT: In the present work, the micronuclei (MN) test was performed in buccal mucosal samples from patients with cancer, with (pre- and post-treatment) and without genotoxic chemotherapy (GC), identified micronucleated cells (MNC) and nuclear abnormalities (binucleated cells (BN), pycnosis (PN), “broken-egg” (BE), condensed chromatin (CC), karyorrhexis (KR), and karyolysis (KL)).The objective was to evaluate the genotoxicity of cisplatin+5-Fluorouracil (5-FU), carboplatin (CBP)+5-Fluorouracil, and ifosfamide (IFO)+epirubicine (EPI) regimens.The ifosfamide+epirubicine regimen described here produced a micronucleogenic effect, whereas the regimens using platinum compounds were cytotoxic for buccal mucosal cells, which probably explains the absence of increase of micronucleated cells in these samples compared with basal levels.In patients with cancer (with and without genotoxic chemotherapy), the numbers of micronucleated cells, pycnosis and karyolysis increased, together with a decrease in binucleated cells and chromatin-condensed. On the other hand, as consequence of the cytotoxicity of the drugs, the number of binucleated cells decreased and the number of karyolytic cells increased. These results could be used as a cytotoxicity marker in future studies for different drugs.
    Mutation Research/Genetic Toxicology and Environmental Mutagenesis 08/2003; 539(1-2):177-186. · 2.48 Impact Factor
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    ABSTRACT: Erythropoiesis is a tightly regulated process in which multipotential hematopoietic stem cells produce mature red blood cells. Here we show that deletion of poly(ADP-ribose) polymerase-2 (PARP-2) in mice leads to chronic anemia at steady state, despite increased erythropoietin plasma levels, a phenomenon not observed in mice lacking PARP-1. Loss of PARP-2 causes shortened lifespan of erythrocytes and impaired differentiation of erythroid progenitors. In erythroblasts, PARP-2 deficiency triggers replicative stress, as indicated by the presence of micronuclei, the accumulation of γ-H2AX (phospho-histone H2AX) in S-phase cells and constitutive CHK1 and replication protein A phosphorylation. Transcriptome analyses revealed the activation of the p53-dependent DNA-damage response pathways in PARP-2-deficient cells, culminating in the upregulation of cell-cycle and cell death regulators, concomitant with G2/M arrest and apoptosis. Strikingly, while loss of the proapoptotic p53 target gene Puma restored hematocrit levels in the PARP-2-deficient mice, loss of the cell-cycle regulator and CDK inhibitor p21 leads to perinatal death by exacerbating impaired fetal liver erythropoiesis in PARP-2-deficient embryos. Although the anemia displayed by PARP-2-deficient mice is compatible with life, mice die rapidly when exposed to stress-induced enhanced hemolysis. Our results pinpoint an essential role for PARP-2 in erythropoiesis by limiting replicative stress that becomes essential in the absence of p21 and in the context of enhanced hemolysis, highlighting the potential effect that might arise from the design and use of PARP inhibitors that specifically inactivate PARP proteins.Cell Death and Differentiation advance online publication, 12 December 2014; doi:10.1038/cdd.2014.202.
    Cell death and differentiation. 12/2014;
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    ABSTRACT: ABSTRACT Genotoxicity and cytotoxicity were evaluated in peripheral blood of mice CD-1 exposed to heavy metals: chromium and thallium (Cr [VI] y Tl [I]). Groups of five animals were treated intraperitoneally with 20 mg/kg of CrO3 or with 30 mg/kg de Tl2SO4. The genetic damage was determined by the kinetic of micronucleus (MN) and apoptosis induction, while the cellular toxicity by the relationship between the polychromatic/normochromatic erythrocytes (EPC/ENC) and cell viability. Evaluations were performed at 0 h, 24 h , 48 h and 72 h after treatment. The results had shown a significant increment in the MN, apoptotic cells and non-viable cells with both treatments. Particularly, the cell and general toxicity was increased in mice exposed to Tl2SO4. Based on the results, it can be suggested that the exposition to metal compounds such as Cr (VI) and Tl (I) represent a genetic and cytotoxic risk for the human populations.
    Acta Universitaria Multidisciplinary Scientific Journal. 01/2014; 24:52-57.