Efeitos da exposição gestacional, lactacional e juvenil às dietas com deficiência e suplementação de zinco e suscetibilidade a carcinogênese da mama em fêmeas Sprague-Dawley
Carregando...
Arquivos
Data
2016-02-24
Autores
Silva, Flávia Regina Moraes da [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O presente estudo teve como objetivo avaliar se a ingestão de dietas com deficiência ou suplementação de zinco, durante as fases de gestação, lactação e juvenil, interfere no desenvolvimento das glândulas mamárias e na susceptibilidade ao desenvolvimento de carcinogênese mamária induzida pela 7,12-dimetilbenz(a)antraceno (DMBA) em ratas da linhagem Sprague-Dawley (SD). Duas gerações, mães e prole de fêmeas receberam dietas com níveis adequados (35mg/Kg dieta), deficientes (3mg/Kg dieta) ou com suplementação (180mg/Kg dieta) de zinco durante a gestação e lactação. Após o desmame, as proles de fêmeas receberam as mesmas dietas das mães até o dia pós-natal (DPN) 51 ou 53. No DPN 51 fêmeas SD foram eutanasiadas para remoção das glândulas mamárias abdominais (D e E) ou receberam dose única de DMBA (50mg/kg; i.g.) para iniciação da carcinogênese e eutanasiadas no DPN 53 ou DPN 180. No dia DPN 53 as glândulas foram processadas para análises histológicas e imunoistoquímicas, e avaliação da expressão de genes relacionados a dano e reparo de DNA, apoptose, ciclo celular e sinalização de genes relacionados ao receptor de estrógeno e p53, por RT-qPCR com sistema Taqman Low density array (TLDA). Os tumores coletados ao longo do experimento e no DPN 180 foram processados para avaliação histológica. As fêmeas alimentadas com dieta deficiente de zinco apresentaram redução significativa no peso corpóreo nos DPNs 0, 10, 21 e 51. O número médio de brotos terminais (TEBs), ductos terminais (TEDs) e lóbulos alveolares (ABLs) mamários não diferiram entre as proles dos três grupos experimentais. No DPN 53, os índices de proliferação nas células epiteliais mamárias foram significativamente maiores no grupo que recebeu suplementação de zinco em relação ao grupo controle, enquanto os índices de células epiteliais em apoptose e RE-α positivas não diferiram entre os grupos. Além disso, a suplementação de zinco reduziu significativamente a expressão dos genes Api5 e Ercc1, que atuam como inibidor de apoptose e reparo de DNA, respectivamente. No DPN 180, tanto a deficiência quanto a suplementação de zinco na dieta não alteraram a latência, incidência, multiplicidade ou volume dos tumores mamários induzidos pela DMBA em relação ao grupo controle. No entanto, a suplementação de zinco aumentou o número total de tumores em 72% quando comparado aos demais grupos. Portanto a suplementação de zinco durante as fases iniciais da vida e perído juvenil aumentou marginalmente a suscetibilidade ao desenvolvimento de tumores mamários.
The present study was designed to evaluate whether dietary intake with zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interfere the development of mammary glands and susceptibility to the mammary carcinogenesis induced by 7,12-dimethylbenzanthracene (DMBA) in female rats Sprague-Dawley (SD) rats. Two generations, dams and female offspring received dietary with zinc levels adequate (35 mg/kg diet), deficiency (3 mg/kg diet) or supplementation (180 mg/kg diet) during pregnancy and lactation. After weaning, the females offspring received the same diets as their dams until post natal day (PND) 51 or 53. On PND 51, females SD were euthanized for removal of the mammary glands (right and left) or received a single dose of DMBA (50mg/kg, ig) for initiation of mammary carcinogenesis and euthanized on PND 53 or PND 180. On PND 53, mammary glands were processed for histological and immunohistochemical analyses, as well as evaluation of the expression of genes related to DNA damage and repair, apoptosis, cell cycle and signaling related to estrogen receptor and p53 by RT-qPCR with Taqman Low density array system (TLDA). Tumors collected throughout experiment or on PND 180 were processed for histological evaluation. The females fed with dietary zinc deficiency presented a significant reduction in body weight on PND 0, 10, 21 e 51. The mean number of the terminal buds (TEBs), terminal ducts (TEDs) and alveolar lobe (ABLs) in mammary gland did not differ among offspring of the three groups. On PND 53 the indexes of proliferation in the mammary glands epithelial cells were significantly higher in the zinc supplementation group in relation to the control group, while the indexes of apoptosis epithelial cell and positive ER-α did not differ among the groups. Also, dietary zinc supplementation significantly reduced the expression of the Api5 and Ercc1 genes related to apoptosis inhibitor and DNA repair, respectively. On PND 180 both dietary zinc deficiency as supplementation did not change the, latency, incidence, multiplicity or volume of DMBA-induced mammary tumors in relation to the control group. However, dietary zinc supplementation increased the total number of tumors in 72% compared to others groups. Therefore zinc supplementation during the early life and juvenile period marginally increased the susceptibility to the mammary tumors development.
The present study was designed to evaluate whether dietary intake with zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interfere the development of mammary glands and susceptibility to the mammary carcinogenesis induced by 7,12-dimethylbenzanthracene (DMBA) in female rats Sprague-Dawley (SD) rats. Two generations, dams and female offspring received dietary with zinc levels adequate (35 mg/kg diet), deficiency (3 mg/kg diet) or supplementation (180 mg/kg diet) during pregnancy and lactation. After weaning, the females offspring received the same diets as their dams until post natal day (PND) 51 or 53. On PND 51, females SD were euthanized for removal of the mammary glands (right and left) or received a single dose of DMBA (50mg/kg, ig) for initiation of mammary carcinogenesis and euthanized on PND 53 or PND 180. On PND 53, mammary glands were processed for histological and immunohistochemical analyses, as well as evaluation of the expression of genes related to DNA damage and repair, apoptosis, cell cycle and signaling related to estrogen receptor and p53 by RT-qPCR with Taqman Low density array system (TLDA). Tumors collected throughout experiment or on PND 180 were processed for histological evaluation. The females fed with dietary zinc deficiency presented a significant reduction in body weight on PND 0, 10, 21 e 51. The mean number of the terminal buds (TEBs), terminal ducts (TEDs) and alveolar lobe (ABLs) in mammary gland did not differ among offspring of the three groups. On PND 53 the indexes of proliferation in the mammary glands epithelial cells were significantly higher in the zinc supplementation group in relation to the control group, while the indexes of apoptosis epithelial cell and positive ER-α did not differ among the groups. Also, dietary zinc supplementation significantly reduced the expression of the Api5 and Ercc1 genes related to apoptosis inhibitor and DNA repair, respectively. On PND 180 both dietary zinc deficiency as supplementation did not change the, latency, incidence, multiplicity or volume of DMBA-induced mammary tumors in relation to the control group. However, dietary zinc supplementation increased the total number of tumors in 72% compared to others groups. Therefore zinc supplementation during the early life and juvenile period marginally increased the susceptibility to the mammary tumors development.
Descrição
Palavras-chave
Carcinogênese mamária, Rato, Deficiência de zinco, Suplementação de zinco, Mammary carcinogenesis, Rat, Zinc deficency, Zinc supplementation