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1.
J Perinatol ; 26(7): 423-7, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16688205

ABSTRACT

OBJECTIVE: To determine sildenafil citrate (SC) genotoxicity and cytotoxicity in the Callithrix jacchus. STUDY DESIGN: Fifteen organisms were assigned to one of three groups as follows: experimental (25 mg/kg of SC); negative control (glucose solution 5%); and positive control (3 mg/kg of cytocine arabinoside). Systemic hemodynamic changes were monitored in each animal before and after each treatment. A drop of blood was obtained before and after the treatment at 24-120 h. Smears were made and the frequency of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes (PCE) was counted. RESULTS: No significant differences in MNE, MNPCE and PCE were found in the group that received sildenafil and negative control. A significant increase in genotoxicity and cytotoxicity was observed in the positive control group. No changes were observed in systemic hemodynamic changes. CONCLUSION: The macro-dose of SC lacks genotoxic, cytotoxic or systemic hemodynamic changes effects in this species.


Subject(s)
3',5'-Cyclic-GMP Phosphodiesterases/antagonists & inhibitors , Chromosome Aberrations/chemically induced , Micronuclei, Chromosome-Defective/chemically induced , Piperazines/toxicity , Vasodilator Agents/toxicity , Administration, Oral , Animals , Blood Pressure/drug effects , Callithrix , Disease Models, Animal , Erythrocytes/pathology , Heart Rate/drug effects , Mutagenicity Tests , Piperazines/administration & dosage , Purines , Random Allocation , Sildenafil Citrate , Sulfones , Vasodilator Agents/administration & dosage
2.
Mutat Res ; 565(1): 91-101, 2004 Dec 31.
Article in English | MEDLINE | ID: mdl-15630804

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 explain 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 MNC, PN, KR, total nuclear abnormalities and KL increased, together with a decrease in BN cells and CC. 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 the future studies for different drugs.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Aged , Carboplatin/administration & dosage , Carboplatin/adverse effects , Cell Nucleus/drug effects , Cell Nucleus/ultrastructure , Cisplatin/administration & dosage , Cisplatin/adverse effects , Epirubicin/administration & dosage , Epirubicin/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Male , Micronucleus Tests/methods , Middle Aged , Mouth Mucosa/drug effects , Mouth Mucosa/ultrastructure
4.
Mutat Res ; 539(1-2): 177-86, 2003 Aug 05.
Article in English | MEDLINE | ID: mdl-12948826

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Aged , Carboplatin/administration & dosage , Carboplatin/adverse effects , Cell Nucleus/drug effects , Cell Nucleus/ultrastructure , Cisplatin/administration & dosage , Cisplatin/adverse effects , Epirubicin/administration & dosage , Epirubicin/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Male , Micronucleus Tests/methods , Middle Aged , Mouth Mucosa/drug effects , Mouth Mucosa/ultrastructure
5.
Mutat Res ; 494(1-2): 161-7, 2001 Jul 25.
Article in English | MEDLINE | ID: mdl-11423355

ABSTRACT

In our previous report we speculated about the possibility that some species had high levels of spontaneous micronucleated erythrocytes (MNE) just in a juvenile stage, this is, that the MNE diminish as the reticuloendothelial system matures. Here we show this effect in species including rat, rabbit, pig, dog, cat, gray squirrel, lion, giraffe, white-tailed deer, opossum and even human. The number of spontaneous MNE that we found in 43 species is shown, and the proportions of polychromatic and normochromatic. This is our third report on spontaneous MNE in different species. We obtained 189 peripheral blood samples of mammals, birds and reptiles. From 12 species we obtained only one sample, and 16 were reported previously, but now the size of the sample has been increased. The species with the highest spontaneous MNE were the Vietnamese potbelly pig (with the highest MNE number), Bengal tiger, capuchin monkey, puma, ferret, owl, hedgehog, squirrel monkey, pig and white-tailed deer. These species could be used as monitors for genotoxic events.


Subject(s)
Aging/blood , Erythrocytes/ultrastructure , Micronuclei, Chromosome-Defective/ultrastructure , Micronucleus Tests , Animals , Birds , Humans , Infant, Newborn , Infant, Premature , Mammals , Reptiles , Species Specificity
6.
Environ Mol Mutagen ; 37(2): 173-7, 2001.
Article in English | MEDLINE | ID: mdl-11246224

ABSTRACT

In some species, in which the human is included, the influence of age in the variation in the number of micronucleated erythrocytes (MNE) is known. In the present work we show how the process of aging influences the number of spontaneous MNE in the gray squirrel (Sciurus aureogaster). Because of the difficulty of knowing the age of each animal, 69 animals were weighed at their arrival to the laboratory and at the start of sample taking, with the supposition that the heaviest animals were the oldest and those with the lightest weight were the youngest. The major number of MNE was found in the younger animals, whereas the adults displayed less MNE (P < 0.0001). A group of 11 animals were sampled every 15 days over a period of 6 months, and the number of MNE were found to decrease with an increment in the weight in conformity with the time elapsed. These results showed that in the gray squirrel, the number of spontaneous MNE in peripheral blood depend on age. An additional interesting datum about the increment of MNE after the administration of colchicine is shown.


Subject(s)
Colchicine/administration & dosage , Erythrocyte Aging/drug effects , Sciuridae/blood , Animals , Micronuclei, Chromosome-Defective
7.
Mutat Res ; 467(1): 99-103, 2000 Apr 13.
Article in English | MEDLINE | ID: mdl-10771274

ABSTRACT

The normal numbers of micronucleated erythrocytes (MNE) observed in peripheral blood samples differ among species. This depends on the effectiveness of the spleen (or the rest of the reticuloendothelial system) to withdraw them from circulation. In our previous report, we assessed the number of MNE in the peripheral blood of 35 mammalian species. Here we show the results observed in 54 species including mammals, reptiles and birds. We obtained 212 peripheral blood samples from different species. In 14 species, only one individual was studied. Slides were stained with acridine orange. The total number of MNE (normo and polychromatic) in 10,000 erythrocytes per animal are shown. The species that display the higher MNE were: ocelote, lynx, owl, gray squirrel, hedgehog, lion, orange fronted parakeet and common barn owl. For this reason, these species could be tested as monitors for genotoxic events. Another interesting observation was that in the gray squirrel, we found the highest values of MNE in the smaller (younger) animals when compared with the larger (older) of the same species.


Subject(s)
Erythrocytes/pathology , Micronuclei, Chromosome-Defective/pathology , Micronucleus Tests , Age Factors , Aging , Animals , Birds , Environmental Pollutants/toxicity , Erythrocytes/ultrastructure , Mammals , Mutagens/toxicity , Reference Values , Reptiles , Species Specificity
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