RESUMO
Most women with breast cancer can become pregnant and give birth while undergoing radiation therapy and breastfeeding is generally not contraindicated. The induction of long-lived reactive species in proteins, such as casein by X-ray radiation and DNA damage to unexposed organisms, has been shown when ingesting irradiated cheese. To determine whether exposing lactating rats to X-rays increases the number of micronucleated erythrocytes (MNEs) in peripheral blood of their unexposed or breastfeeding rat pups, 15 female Wistar rats were divided into three groups: Negative control; Experimental group exposed to X-rays, and group exposed to X-rays plus vitamin C. The mothers of groups 2 and 3 were irradiated for three consecutive days after giving birth, returning them to their respective cages each time to continue lactation. A blood sample was taken from the mothers and pups at 0, 24, and 48 hr. Blood smears were stained with acridine orange to analyze MNEs. In mother rats, the frequency of micronucleated polychromatic erythrocytes (MNPCEs) increased significantly at 24 and 48 hr in both study groups exposed to radiation. Likewise, in rat pups the MNPCE and MNE frequencies increased in both groups with radiation and radiation plus vitamin C at 24 and 48 hr, and a protection from vitamin C was observed. In conclusion, the genotoxic damage produced in rat pups that were lactated by mothers irradiated with X-rays is possibly due to the effect of long-lived reactive species that were formed in the breast milk of female Wistar rats during the irradiation process.
Assuntos
Dano ao DNA/genética , Eritrócitos/efeitos da radiação , Lactação/efeitos da radiação , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Animais , Neoplasias da Mama/complicações , Neoplasias da Mama/radioterapia , Dano ao DNA/efeitos da radiação , Eritrócitos/patologia , Feminino , Lactação/genética , Masculino , Testes para Micronúcleos , Mães , Gravidez , Ratos , Ratos Wistar , Raios X/efeitos adversosRESUMO
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 , RatosRESUMO
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 , Oxigenoterapia Hiperbárica , Hiperbilirrubinemia/terapia , Recém-Nascido , Recém-Nascido Prematuro , Masculino , FototerapiaRESUMO
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-DawleyRESUMO
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/metabolismoRESUMO
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/genéticaRESUMO
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 WistarRESUMO
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.