Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus)

Detalhes bibliográficos
Autor(a) principal: Meireles, José Roberto Cardoso
Data de Publicação: 2012
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UEFS
Texto Completo: http://tede2.uefs.br:8080/handle/tede/1041
Resumo: The use of anabolic androgenic steroids (AAS) aiming the rapid development of muscle mass has increased in several populations worldwide. In spite the potential benefits of these drugs in treating some diseases their indiscriminate use can cause damage to health, such as alterations in cardiovascular and liver functions. Data from literature are controversial in relation to the association between AAS use and cancer development. Considering that cancer is a genetic disease, resulting from alterations in genes involved with the cellular proliferation and differentiation, or in genes compromised with DNA repair and apoptosis, this study aimed to evaluate the genotoxic potential of three ASS: deca-durabolin®, deposteron® and durateston® using the micronucleus test in bone marrow of rodents. Swiss male mice six to eight weeks of age were treated, by intramuscular injection, with each drug at three different concentrations: clinical dose (DC), clinical dose concentrated five times (5X DC) and concentrated ten times the clinical dose (DC 10X). One group of animals was treated with cyclophosphamide as a positive control (CP) and another group (negative control) with corn oil (CN). Animals were sacrificed 24h, 48h and 72h after treatment and immediately bone marrow was removed, processed and prepared smears on slides for microscopy. Micronuclei were computed in 1000 polychromatic erythrocytes for assessment of chromosomal damage. Cytotoxicity was assessed by determining the ratio PCE-NCE (erythrocyte normochromatic) in 200 erythrocytes/animal. The occurrence of micronuclei was significantly higher in the animals treated with drugs at higher concentration (DC 10X) compared to the other groups, except for the positive control. Moreover, the drugs in this concentration also induced cell cycle delay revealing cytotoxic effects. These results indicate that AAS induces, in mice, chromosomal damage and cytotoxicity in concentration dependence.
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spelling Cerqueira, Eneida de Moraes Macílio0410445650450786750510http://lattes.cnpq.br/9300910391617261Meireles, José Roberto Cardoso2020-04-08T23:32:19Z2012-10-28MEIRELES, José Roberto Cardoso. Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus). 2012. 65 f. Tese (Doutorado Acadêmico em Biotecnologia)- Universidade Estadual de Feira de Santana, Feira de Santana, 2012.http://tede2.uefs.br:8080/handle/tede/1041The use of anabolic androgenic steroids (AAS) aiming the rapid development of muscle mass has increased in several populations worldwide. In spite the potential benefits of these drugs in treating some diseases their indiscriminate use can cause damage to health, such as alterations in cardiovascular and liver functions. Data from literature are controversial in relation to the association between AAS use and cancer development. Considering that cancer is a genetic disease, resulting from alterations in genes involved with the cellular proliferation and differentiation, or in genes compromised with DNA repair and apoptosis, this study aimed to evaluate the genotoxic potential of three ASS: deca-durabolin®, deposteron® and durateston® using the micronucleus test in bone marrow of rodents. Swiss male mice six to eight weeks of age were treated, by intramuscular injection, with each drug at three different concentrations: clinical dose (DC), clinical dose concentrated five times (5X DC) and concentrated ten times the clinical dose (DC 10X). One group of animals was treated with cyclophosphamide as a positive control (CP) and another group (negative control) with corn oil (CN). Animals were sacrificed 24h, 48h and 72h after treatment and immediately bone marrow was removed, processed and prepared smears on slides for microscopy. Micronuclei were computed in 1000 polychromatic erythrocytes for assessment of chromosomal damage. Cytotoxicity was assessed by determining the ratio PCE-NCE (erythrocyte normochromatic) in 200 erythrocytes/animal. The occurrence of micronuclei was significantly higher in the animals treated with drugs at higher concentration (DC 10X) compared to the other groups, except for the positive control. Moreover, the drugs in this concentration also induced cell cycle delay revealing cytotoxic effects. These results indicate that AAS induces, in mice, chromosomal damage and cytotoxicity in concentration dependence.O uso de esteróides anabólicos androgênicos (EAA), visando o desenvolvimento rápido de massa muscular tem aumento em várias populações do mundo. Apesar dos benefícios potenciais destes medicamentos no tratamento de algumas doenças seu uso indiscriminado pode causar prejuízos para a saúde, como alterações cardiovasculares e nas funções hepáticas. Dados da literatura são controversos em relação à associação entre o uso de EAA e desenvolvimento de câncer. Considerando que o câncer é uma doença genética, decorrente de alterações em genes envolvidos com a proliferação e diferenciação celular, ou em genes envolvidos no reparo do DNA e apoptose, este estudo objetivou avaliar o potencial genotóxico dos EAA deca-durabolin®, deposteron® e durateston® usando o teste de micronúcleo em medula óssea de roedor. Camundongos machos Swiss com seis a oito semanas de idade foram tratados, por meio de injeção intramuscular, com cada droga em três concentrações diferentes: dose clínica (DC), dose clínica concentrada cinco vezes (DC 5X) e dose clínica concentrada dez vezes (DC 10X). Um grupo de animais tratado com ciclofosfamida foi utilizado como controle positivo (CP) e outro grupo (controle negativo), com óleo de milho (CN). Os animais foram sacrificados 24h, 48h e 72h depois do tratamento e imediatamente a medula óssea foi removida, processada e preparados esfregaços em lâminas para microscopia. Micronúcleos foram computados em 1000 eritrócitos policromáticos (PCE) para avaliação de danos cromossômicos. Citotoxicidade foi avaliada pela determinação da relação PCE-NCE (eritrócito normocromático) em 200 eritrócitos/animal. A ocorrência de micronúcleo foi significativamente maior nos animais tratados com as drogas em maior concentração (DC 10X) em comparação com os outros grupos, exceto para o controle positivo. Além disso, esta concentração também induziu atraso no ciclo celular revelando efeito citotóxico. Estes resultados indicam que os EAA analisados induzem, em camundongos, lesões cromossômicas e são citotóxicos na dependência da concentração.Submitted by Ricardo Cedraz Duque Moliterno (ricardo.moliterno@uefs.br) on 2020-04-08T23:32:19Z No. of bitstreams: 1 Tese_José ROberto.pdf: 2978108 bytes, checksum: 4ca0b2a689a85e74bc5cc72c1787ac48 (MD5)Made available in DSpace on 2020-04-08T23:32:19Z (GMT). No. of bitstreams: 1 Tese_José ROberto.pdf: 2978108 bytes, checksum: 4ca0b2a689a85e74bc5cc72c1787ac48 (MD5) Previous issue date: 2012-10-28application/pdfporUniversidade Estadual de Feira de SantanaDoutorado Acadêmico em BiotecnologiaUEFSBrasilDEPARTAMENTO DE CIÊNCIAS BIOLÓGICASEsteróides anabolizantesMicronúcleoGenotoxicidadeCitotoxicidadeAnabolic steroidsMicronucleusGenotoxicityCytotoxicityGENETICA::MUTAGENESEAvaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus)info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis-68152692297897915436006006005026123383450589282-4315821173933878065info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UEFSinstname:Universidade Estadual de Feira de Santana (UEFS)instacron:UEFSORIGINALTese_José ROberto.pdfTese_José ROberto.pdfapplication/pdf2978108http://tede2.uefs.br:8080/bitstream/tede/1041/2/Tese_Jos%C3%A9+ROberto.pdf4ca0b2a689a85e74bc5cc72c1787ac48MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82089http://tede2.uefs.br:8080/bitstream/tede/1041/1/license.txt7b5ba3d2445355f386edab96125d42b7MD51tede/10412020-04-08 20:32:19.256oai:tede2.uefs.br:8080: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.uefs.br:8080/PUBhttp://tede2.uefs.br:8080/oai/requestbcuefs@uefs.br|| bcref@uefs.br||bcuefs@uefs.bropendoar:2020-04-08T23:32:19Biblioteca Digital de Teses e Dissertações da UEFS - Universidade Estadual de Feira de Santana (UEFS)false
dc.title.por.fl_str_mv Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus)
title Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus)
spellingShingle Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus)
Meireles, José Roberto Cardoso
Esteróides anabolizantes
Micronúcleo
Genotoxicidade
Citotoxicidade
Anabolic steroids
Micronucleus
Genotoxicity
Cytotoxicity
GENETICA::MUTAGENESE
title_short Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus)
title_full Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus)
title_fullStr Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus)
title_full_unstemmed Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus)
title_sort Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus)
author Meireles, José Roberto Cardoso
author_facet Meireles, José Roberto Cardoso
author_role author
dc.contributor.advisor1.fl_str_mv Cerqueira, Eneida de Moraes Macílio
dc.contributor.advisor1ID.fl_str_mv 04104456504
dc.contributor.authorID.fl_str_mv 50786750510
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/9300910391617261
dc.contributor.author.fl_str_mv Meireles, José Roberto Cardoso
contributor_str_mv Cerqueira, Eneida de Moraes Macílio
dc.subject.por.fl_str_mv Esteróides anabolizantes
Micronúcleo
Genotoxicidade
Citotoxicidade
topic Esteróides anabolizantes
Micronúcleo
Genotoxicidade
Citotoxicidade
Anabolic steroids
Micronucleus
Genotoxicity
Cytotoxicity
GENETICA::MUTAGENESE
dc.subject.eng.fl_str_mv Anabolic steroids
Micronucleus
Genotoxicity
Cytotoxicity
dc.subject.cnpq.fl_str_mv GENETICA::MUTAGENESE
description The use of anabolic androgenic steroids (AAS) aiming the rapid development of muscle mass has increased in several populations worldwide. In spite the potential benefits of these drugs in treating some diseases their indiscriminate use can cause damage to health, such as alterations in cardiovascular and liver functions. Data from literature are controversial in relation to the association between AAS use and cancer development. Considering that cancer is a genetic disease, resulting from alterations in genes involved with the cellular proliferation and differentiation, or in genes compromised with DNA repair and apoptosis, this study aimed to evaluate the genotoxic potential of three ASS: deca-durabolin®, deposteron® and durateston® using the micronucleus test in bone marrow of rodents. Swiss male mice six to eight weeks of age were treated, by intramuscular injection, with each drug at three different concentrations: clinical dose (DC), clinical dose concentrated five times (5X DC) and concentrated ten times the clinical dose (DC 10X). One group of animals was treated with cyclophosphamide as a positive control (CP) and another group (negative control) with corn oil (CN). Animals were sacrificed 24h, 48h and 72h after treatment and immediately bone marrow was removed, processed and prepared smears on slides for microscopy. Micronuclei were computed in 1000 polychromatic erythrocytes for assessment of chromosomal damage. Cytotoxicity was assessed by determining the ratio PCE-NCE (erythrocyte normochromatic) in 200 erythrocytes/animal. The occurrence of micronuclei was significantly higher in the animals treated with drugs at higher concentration (DC 10X) compared to the other groups, except for the positive control. Moreover, the drugs in this concentration also induced cell cycle delay revealing cytotoxic effects. These results indicate that AAS induces, in mice, chromosomal damage and cytotoxicity in concentration dependence.
publishDate 2012
dc.date.issued.fl_str_mv 2012-10-28
dc.date.accessioned.fl_str_mv 2020-04-08T23:32:19Z
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dc.identifier.citation.fl_str_mv MEIRELES, José Roberto Cardoso. Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus). 2012. 65 f. Tese (Doutorado Acadêmico em Biotecnologia)- Universidade Estadual de Feira de Santana, Feira de Santana, 2012.
dc.identifier.uri.fl_str_mv http://tede2.uefs.br:8080/handle/tede/1041
identifier_str_mv MEIRELES, José Roberto Cardoso. Avaliação genotóxica de esteróides anabolizantes sintéticos com uso do teste de micronúcleo em medula óssea de camundongos (Mus musculus). 2012. 65 f. Tese (Doutorado Acadêmico em Biotecnologia)- Universidade Estadual de Feira de Santana, Feira de Santana, 2012.
url http://tede2.uefs.br:8080/handle/tede/1041
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dc.publisher.program.fl_str_mv Doutorado Acadêmico em Biotecnologia
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