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1.
Ann Clin Lab Sci ; 48(2): 152-157, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29678840

RESUMO

The aim of the study was to determine if amniotic fluid cells of rats can be used to provide evidence of genotoxicity. In order to do that micronuclei formation was induced in rats during pregnancy after treatment with cyclophosphamide (CP), at different CP doses. On gestational day 19, we collected the amniotic fluid and determined the frequency of micronucleated cells (MNCs) from the offspring. Samples were centrifuged and placed on clean slides. The smears were observed with an epifluorescence microscope. The number of MNCs in 2000 cells per pregnant rat was counted. The fetus weight and size were recorded and provided evidence of DNA damage caused by CP administration to their mothers. A significantly greater number of MNCs was observed only for the medium CP dose (P<0.01) and the high CP dose (P<0.02) groups versus the negative control group. Birth defects produced by the administration of the CP were evident in the CP-treated groups. This study showed an alternative method to determine if compounds administrated to pregnant rat cause damage to the genetic material of their offspring. Using micronuclei testing of amniotic fluid cells enables us to determine in one test the genotoxicity and the teratogenic potential of a compound.


Assuntos
Líquido Amniótico/efeitos dos fármacos , Ciclofosfamida/toxicidade , Imunossupressores/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Animais Recém-Nascidos , Ciclofosfamida/farmacologia , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Testes para Micronúcleos , Gravidez , Lesões Pré-Natais/induzido quimicamente , Ratos , Ratos Wistar , Estatísticas não Paramétricas
2.
Biomed Res Int ; 2016: 9161648, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28018917

RESUMO

Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs) and micronucleated polychromatic erythrocytes (MNPCEs) in the samples from pups in the experimental groups (P < 0.02) and increased MNPCE frequencies in the samples from the dams (P < 0.05). These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects.


Assuntos
Aleitamento Materno , Eritrócitos/efeitos dos fármacos , Relações Materno-Fetais/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Animais , Colchicina/toxicidade , Ciclofosfamida/toxicidade , Citarabina/toxicidade , Feminino , Humanos , Testes de Mutagenicidade , Ratos
3.
J Photochem Photobiol B ; 165: 141-146, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27792890

RESUMO

Exposure to ultraviolet-A (UVA) light can accidentally cause adverse effects in the skin and eyes. UVA induces DNA damage directly by creating pyrimidine dimers or by the formation of reactive oxygen species that can indirectly affect DNA integrity. UVA radiation is emitted by lamps from everyday devices. In adult rats, micronucleated erythrocytes (MNE) are removed from the circulation by the spleen. However, in newborn rats, MNE have been observed in peripheral blood erythrocytes. The objective of this study was to use micronucleus tests to evaluate the DNA damage caused in newborn rats exposed to UVA light from three different types of UVA lamps obtained from commonly used devices: counterfeit detectors, insecticide devices, and equipment used to harden resins for artificial nails. Rat neonates were exposed to UVA lamps for 20min daily for 6days. The neonates were sampled every third day, and the numbers of MNE and micronucleated polychromatic erythrocytes (MNPCE) in the peripheral blood were determined. The rat neonates exposed to the three types of UVA lamps showed increased numbers of MNE and MNPCE from 48h to 144h (P<0.05 and P<0.001 respectively). However, no relationship was observed between the number of MNE and the wattage of the lamps. In conclusion, under these conditions, UVA light exposure induced an increase in MNE without causing any apparent damage to the skin.


Assuntos
Núcleo Celular/efeitos da radiação , Eritrócitos/efeitos da radiação , Raios Ultravioleta , Animais , Animais Recém-Nascidos , Testes para Micronúcleos , Ratos
4.
Artigo em Inglês | MEDLINE | ID: mdl-25868130

RESUMO

Pregnant hairless rat dams were exposed to ultraviolet-A light (UVA) to induce micronucleated erythrocytes (MNE) in their fetuses. The control group was exposed to conventional light; the experimental groups were exposed to UVA (365nm) during gestational days 16-21. In some cases, ascorbic acid (Asc) was administered in the drinking water from gestational day 15 until delivery. Dams were sampled at 48-h intervals during gestation, from day 16 until delivery. Blood was also obtained from neonates at birth; MNE, micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) were scored. Increased MNE and MNPCE were observed in neonates born to mothers exposed to UVA for 40, 80 or 160min, compared to the control group. Asc treatment reduced MNE and MNPCE induction.


Assuntos
Eritrócitos/efeitos da radiação , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Efeitos Tardios da Exposição Pré-Natal/genética , Raios Ultravioleta , Animais , Animais Recém-Nascidos , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Masculino , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Testes para Micronúcleos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Ratos Pelados , Fatores de Tempo
5.
J Photochem Photobiol B ; 141: 283-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25463679

RESUMO

In previous studies, exposure to phototherapy, but not oxygen therapy, resulted in damage to genetic material in newborns. The objective of this study was to determine whether micronucleated erythrocytes (MNE) increased in preterm newborns (PNBs) who were exposed to blue light phototherapy lamps. MNE of mature organisms are rapidly eliminated by the spleen, and the presence of MNE has been related to immaturity in some species. Furthermore, PNBs present spontaneous MNE. Blood samples were taken from 17 PNBs at birth to establish baseline frequencies (0 h). After beginning blue light phototherapy, blood samples were obtained from 11 of these PNBs at 24-h intervals for 96 h, after the baseline sample. MNE and micronucleated polychromatic erythrocytes (MNPCE) were counted. The basal values of MNE and MNPCE from 17 PNBs were 0.62 ± 0.48 and 1.52 ± 1.28 (‰), respectively, and no increase in MNE or MNPCE was observed in the serial samples of 11 PNBs exposed to blue light and oxygen therapies, though previous studies reported increases using other types of lamps. In conclusion, under the conditions described no increase in the number of MNE or MNPCE was observed in the peripheral blood of PNBs exposed to blue light phototherapy.


Assuntos
DNA/metabolismo , Luz , DNA/química , Eritrócitos/citologia , Eritrócitos/efeitos da radiação , Feminino , Idade Gestacional , Humanos , Oxigenação Hiperbárica , Hiperbilirrubinemia/terapia , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Fototerapia
6.
Food Chem Toxicol ; 50(8): 2760-5, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22683486

RESUMO

Pirfenidone is a non-steroidal antifibrotic compound that has been proposed in clinical protocols and experimental studies as a pharmacological treatment for fibroproliferative diseases. The objective of this study was to determine the genotoxicity or cytotoxicity of three doses of pirfenidone using the micronuclei test in peripheral blood erythrocytes of rodent models. Pirfenidone was administered orally to Balb-C mice for 3 days, and also was administered topically to hairless Sprague Dawley rats during the final stage of gestation. Mice were sampled every 24 h over the course of 6 days; pregnant rats were sampled every 24 h during the last 6 days of gestation, and pups were sampled at birth. Blood smears were analyzed and the frequencies of micronucleated erythrocytes (MNEs), micronucleated polychromatic erythrocytes (MNPCEs), and the proportion of polychromatic erythrocytes (PCEs), were recorded in samples from mice, pregnant rats and rat neonates. Increases in MN frequencies (p<0.03) were noted only in the positive control groups. No genotoxic effects or decreased PCE values were observed neither in newborn rats transplacentally exposed to pirfenidone, or in two adult rodent models when pirfenidone was administered orally or topically.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Eritrócitos/efeitos dos fármacos , Testes para Micronúcleos , Mutagênicos/toxicidade , Piridonas/toxicidade , Animais , Eritrócitos/ultraestrutura , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Gravidez , Ratos , Ratos Sprague-Dawley
7.
J Photochem Photobiol B ; 107: 79-83, 2012 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-22209030

RESUMO

Preterm newborns (PNBs) have an immature antioxidant defense system, and this makes them more susceptible to oxidative stress generated by postnatal treatments. The objective was to determine whether micronucleated erythrocytes increase in PNB by postnatal treatments such as oxygentherapy and phototherapy. We counted micronucleated erythrocytes and micronucleated polychromatic erythrocytes as DNA damage in 72 blood samples of PNB at 26-36 weeks of gestation, taken between 1 and 84 h after birth. We assume that more time passed between sampling and birth would correspond to greater time of exposure to oxygen (37 cases) and phototherapy plus oxygen (35 cases). In the PNB only exposed to oxygen, the differences were not significant, while there was a significant increase in micronucleated polychromatic erythrocytes with increasing exposure time in those treated with phototherapy plus oxygen. In conclusion, our results suggest that the MN increase from phototherapy can be observed in peripheral blood erythrocytes of PNB.


Assuntos
Núcleo Celular/metabolismo , Eritrócitos/patologia , Oxigênio/efeitos adversos , Oxigênio/uso terapêutico , Fototerapia/efeitos adversos , Nascimento Prematuro/sangue , Nascimento Prematuro/terapia , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/efeitos da radiação , Dano ao DNA , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/efeitos da radiação , Feminino , Humanos , Recém-Nascido , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/efeitos da radiação , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Nascimento Prematuro/genética , Nascimento Prematuro/metabolismo
8.
Drug Chem Toxicol ; 34(4): 462-6, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21749197

RESUMO

Topical pimecrolimus is an alternative treatment of atopic dermatitis. However, rare cases of malignancy have been reported with their use. This study was performed to investigate the possible geno- or cytotoxic effect in mouse bone marrow caused by systemic absorption of pimecrolimus 1% cream. In order to determine this, induction of micronucleated erythrocytes (MNE) in mouse peripheral blood was determined after the cutaneous application of three different doses, daily for 5 consecutive days. No differences were found in frequencies of polychromatic erythrocytes, MNE, and micronucleated polychromatic erythrocytes in the different groups of study. In conclusion, under described conditions, no geno- or cytotoxic effects were detected after the cutaneous application of pimecrolimus.


Assuntos
Eritrócitos/efeitos dos fármacos , Imunossupressores/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Tacrolimo/análogos & derivados , Administração Cutânea , Animais , Sobrevivência Celular/efeitos dos fármacos , Eritrócitos/patologia , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes para Micronúcleos , Pomadas , Pele/metabolismo , Absorção Cutânea , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinética , Tacrolimo/toxicidade
9.
Drug Chem Toxicol ; 34(3): 294-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21649484

RESUMO

Methylphenidate (MPH; Ritalin®; Novartis Pharmaceuticals, Inc., Basel, Switzerland) has been prescribed to treat attention deficit/hyperactivity disorder (ADHD) since its approval by the U.S. Food and Drug Administration over 50 years ago. Due to concerns that MPH might induce cytogenetic alterations in children, treatment with this drug has been a controversial issue. In the present study, we assessed the frequency of micronucleated erythrocytes (MNEs), micronucleated polychromatic erythrocytes (MNPCEs), and polychromatic erythrocytes (PCEs) in peripheral blood samples from mice treated with three different doses of MPH (30, 60, or 125 mg/kg). We found no evidence of increased MNEs or MNPCEs, nor did PCEs decline. These results add to the accumulating evidence that MPH does not induce genotoxic or cytotoxic damage.


Assuntos
Eritrócitos/efeitos dos fármacos , Metilfenidato/toxicidade , Mutagênicos/toxicidade , Administração Oral , Animais , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos
10.
Mutat Res ; 634(1-2): 126-34, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17669682

RESUMO

Diabetes mellitus (DM) is associated with a high risk of health complications, mainly due to excessive free radical (FRs) production that could result in an increased frequency of micronuclei. The consumption of antioxidants, like folic acid (FA), may mitigate the effects of the FRs. In the present study, micronucleated polychromatic erythrocyte (MNPCE) frequencies were determined in blood sampled weekly from the tails of pregnant female Wistar rats and pregnant Wistar rats with experimental diabetes that were given unsupplemented diets and diets supplemented with FA. At birth, the pups were sampled to analyze micronucleated erythrocyte (MNE) and MNPCE frequencies. Moreover micronucleated cells (MNCs) were evaluated in buccal mucosa samples taken from 81 healthy adult subjects, 48 patients with DM, and 30 DM patients who were sampled before and after FA treatment. Increases in MNPCE frequencies were significant only at the first sampling (P<0.01 and P<0.03) in pregnant rats with experimental diabetes. In addition, the pups from the diabetic group and from diabetic group treated with FA had higher frequencies of MNEs (P<0.03 and P<0.001, respectively) and MNPCEs (P<0.009 and P<0.05, respectively) than the controls. No differences were found in diabetic rats and newborn rats born to diabetic mothers treated with FA compared with untreated animals. Patients with DM had a higher frequency of MNCs compared with healthy subjects (P<0.001). Also FA reduced the frequency of MNCs in DM patients (P<0.001). The results of this study indicate that diabetes results in elevated frequencies of micronuclei, and that, at least in humans, FA can protect against the elevation.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Ácido Fólico/uso terapêutico , Adulto , Animais , Animais Recém-Nascidos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Suplementos Nutricionais , Feminino , Humanos , Masculino , Testes para Micronúcleos , Gravidez , Gravidez em Diabéticas/tratamento farmacológico , Ratos , Ratos Wistar
11.
Artigo em Inglês | MEDLINE | ID: mdl-17680492

RESUMO

A series of bioindicator organisms for aquatic ecosystems are being maintained under laboratory conditions in order to analyze effects of pollution on aquatic wildlife and potential effects on human health. Growth kinetics of algae Pseudokirchneriella subcapitata was used to evaluate effects of the surfactant nonilphenol (NP). Brachionus calyciflorus was used to set up a model of endocrine disruption using the fungicide vinclozolin (Vc). We exposed salamanders from the genus Ambystoma sp., to different concentrations of both the aneugen colchicine (COL) and the clastogen cyclophosphamide (CP) and we determined the frequency of micronucleated cells (MNC) in their shed skin. The presence of spontaneous micronuclei in peripheral blood erythrocytes from 10 fish species in Lake "La Alberca," Michoacan (Mexico), was evaluated as a possible biological indicator of genotoxic agents. Results confirm the sensivity of Pseudokirchneriella subcapitata to growth kinetics: the range of concentration of NP (20, 200 and 2000 microg L(- 1)) shows an inverted U shape in its maximum growth rate; Dimethyl sulfoxide (DMSO) used as a positive control and to solvate NP induced an inverse stimulatory effect on growth rate in the range of concentrations analyzed (0.0023, 0.023 and 0.23% v v(- 1)). In the use of the rotifer Brachionus calyciflorus, the range of Vc from 0.185 mg L(- 1) to 3 mg L(- 1) clearly showed an inverted U shape characteristic of endocrine disruptions. We were able to use shed skin from Ambystoma sp., to measure MNC frequencies induced either by an aneugenic or a clastogenic compound. The MNC frequency was increased significantly by all doses of COL and CP, administered either as single or repeated exposures. The presence of MNC in the shed skin and the speed of sloughing lead us to propose that the sheds of Ambystoma sp., or other amphibians that slough their skin, as suitable alternative models for detecting genotoxic exposures relevant to aquatic environments. In the survey to determine potential biological fish indicators for genotoxic agents, the frequency of spontaneous micronucleated erythrocytes (MNE) found in the goodeid Xenotoca melanosoma (3.7 +/- 1.6 MNC) and the cichlid Oreochromis aureus (2.0 +/- 1.0 MNC) suggests that these species can be considered as potential biological indicators.


Assuntos
Poluentes Químicos da Água/toxicidade , Animais , Clorófitas/efeitos dos fármacos , Clorófitas/crescimento & desenvolvimento , Colchicina/toxicidade , Ciclofosfamida/toxicidade , Feminino , Peixes , Fungicidas Industriais/toxicidade , Dose Letal Mediana , Masculino , México , Testes para Micronúcleos , Mutagênicos/toxicidade , Oxazóis/toxicidade , Fenóis/toxicidade , Reprodução/efeitos dos fármacos , Rotíferos/efeitos dos fármacos , Rotíferos/fisiologia , Pele/citologia , Urodelos/genética
12.
Avian Pathol ; 35(3): 206-10, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16753611

RESUMO

Nuclear abnormalities in erythrocytes, as micronuclei and nuclear buds (BE), are considered potential biomarkers of genotoxic exposure. We described previously the frequency of spontaneous micronucleated erythrocytes (MNE) in the species Aratinga canicularis. Here, we have used this species to evaluate the induction of MNE and BE by mitomycin-C. Animals were given a single intracoelomic injection of 0, 2, 3 or 4 mg/kg mitomycin-C on two consecutive days. A drop of blood was obtained after 0, 24, 48 and 72 h, and stained smears were used to count micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes with buds (BPCE)/1000 polychromatic erythrocytes. The number of MNE and BE in 10 000 total erythrocytes was also counted. MNPCE and BPCE frequencies were elevated at 24, 48, and 72 h after the administration of the lower dose (P<0.03). At a 3 mg/kg dose, the frequency of MNPCE increased at 48 and 72 h (P<0.04) whereas the number of BPCE increased, but not significantly. Administration of 4 mg/kg mitomycin-C increased the number of MNE observed at 72 h (P<0.03), the number of MNPCE at 48 h (P<0.01) and 72 h (P<0.006), the BE frequency at 72 h (P<0.05), and the frequency of BPCE at 48 and 72 h (P<0.001). While mitomycin-C appears to produce a parallel increase in MNPCE and BPCE frequencies, the MNE seemed to be a more sensitive indicator of genotoxicity than the BE. This suggests that evaluating BE and MNE in routine haematological analysis should be considered to evaluate environmental genotoxic exposure.


Assuntos
Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Dano ao DNA/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Mitomicina/toxicidade , Papagaios , Animais , Núcleo Celular/patologia , Relação Dose-Resposta a Droga , Feminino , Masculino , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/veterinária , Mutagênicos/toxicidade , Papagaios/sangue , Papagaios/genética
13.
Environ Mol Mutagen ; 47(5): 352-6, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16628750

RESUMO

Metronidazole (MTZ) is used for the treatment of many infectious diseases, including vaginal infections. While data indicate that MTZ is mutagenic and induces micronuclei in rodents, there is no information on the genotoxicity of MTZ in epithelial vaginal cells or cervical cells. In the present study, we have instilled MTZ into the vagina of rats and evaluated the micronucleus (MN) frequency in proestrus rat vaginal mucosal cells. The first identified proestrus before treatment was used to establish basal proestrus micronucleated cell (PMNC) frequencies. Rats then were assigned to one of five groups: a negative control, three MTZ treatment groups (30, 50, or 100 mg/kg MTZ), and a positive control treated with 2.5 mg of 5-fluorouracil (5-Fu) per rat. Following treatment for five consecutive days, vaginal cell samples were taken daily until three cycles of estrus were completed. Smears prepared from the samples were evaluated for micronuclei in proestrus cells. No differences were found between the PMNC frequencies of the negative control and the 30 and 50 mg/kg MTZ groups. The group treated with 100 mg/kg MTZ, however, had significantly elevated PMNC frequencies in the first and second proestrus samples, while 5-Fu treatment produced significant increases in PMNC frequency in the second and third proestrus. These results indicate that topical administration of relatively high concentrations of MTZ is genotoxic in rat vaginal mucosa cells.


Assuntos
Anti-Infecciosos/toxicidade , Metronidazol/toxicidade , Vagina/efeitos dos fármacos , Administração Intravaginal , Animais , Feminino , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Membrana Mucosa/efeitos dos fármacos , Mutagênicos/toxicidade , Proestro , Ratos , Ratos Wistar
14.
Environ Mol Mutagen ; 46(4): 253-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15971258

RESUMO

Nonhuman primates are of particular relevance in evaluating the potential toxicity of drugs and environmental agents. We have used previously published information and data from the present study to establish a relationship for New World (NW) and Old World (OW) primates on the basis of the frequency of spontaneous micronucleated erythrocytes (MNEs) observed in peripheral blood. Data on spontaneous MNEs in peripheral blood from 15 species of primates, including humans, indicate that NW primates have significantly (P < 0.01) higher MNE frequencies (group mean, 9.5 +/- 7.3 MNEs/10,000 erythrocytes; range, 0.7-20.5/10,000 erythrocytes) than OW primates (group mean, 1.0 +/- 0.9 MNEs/10,000 erythrocytes; range, 0.0-2.6 MNEs/10,000 erythrocytes). Humans are believed to have developed in the OW, and human MNE frequencies were similar to those described for OW primate species. We selected the common marmoset (Callithrix jacchus), a NW primate, to determine whether therapeutic pediatric doses of Metotrexate (MTX; 2.5 mg/kg), Cyclophosphamide (CP; 5 mg/kg), Cytosine-arabinoside (Ara-C; 3 mg/kg), or 5-Fluorouracil (5-FU; 10 mg/kg), administered daily for two consecutive days, increase the frequency of micronuclei. Micronucleated polychromatic erythrocyte frequencies were increased significantly in groups receiving MTX, CP and Ara-C, while MNE frequencies were increased by the Ara-C treatment. The results of this study indicate that NW primates have higher spontaneous MNE frequencies than OW primates, and because of this, NW primates like the common marmoset, may be suitable for evaluating the genotoxicity of chemical agents.


Assuntos
Callithrix/sangue , Eritrócitos/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Modelos Animais , Mutagênicos/toxicidade , Primatas/sangue , Animais , Antineoplásicos/toxicidade , Ciclofosfamida/toxicidade , Citarabina/toxicidade , Eritrócitos/patologia , Fluoruracila/toxicidade , Humanos , Metotrexato/toxicidade , Testes para Micronúcleos , Testes de Mutagenicidade
15.
Arch Med Res ; 34(2): 141-4, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12700011

RESUMO

BACKGROUND: For topically applied drugs such as 5-fluorouracil (5-FU), dosage is not as precise as for other drug administration pathways. Consequently, quantity of drug delivered may differ among individuals and applications. 5-FU is used in treatment of different diseases and has been reported as a clastogenic compound by micronucleus assay. METHODS: To determine whether 5-FU cream (5% 5-FU) absorbed through skin can produce genotoxic or cytotoxic effect in mouse bone marrow, induction of micronucleated erythrocytes (MNE) in mouse peripheral blood was examined after cutaneous application of 5-FU daily for 5 days. RESULTS: 5-FU cream induced significant micronuclei at doses of 37.5 mg (total weight of cream)/2 cm(2) and 75.0 mg/2 cm(2), as well as cytotoxic effects at doses of 150.0 and 300.0 mg/2 cm(2). CONCLUSIONS: Cutaneous application of 5-FU increased number of MNE in mouse peripheral blood. These data emphasize the importance of using correct dose when applying drugs topically.


Assuntos
Eritrócitos/metabolismo , Fluoruracila/farmacologia , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/metabolismo , Administração Cutânea , Animais , Antimetabólitos Antineoplásicos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes para Micronúcleos , Fatores de Tempo
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