Gestational and lactational exposition to Di-N-butyl-phthalate (DBP) increases inflammation and preneoplastic lesions in prostate of wistar rats after carcinogenic N-methyl-N-nitrosourea (MNU) plus testosterone protocol

Autor(es)

Peixoto, Andre R. ; Santos, Talita M. ; Brandt, Joyce Z. ; Delella, Flavia K. ; Goncalves, Bianca F. ; Campos, Silvana G. P. ; Taboga, Sebastiao R. ; Favaro, Wagner J. ; Domeniconi, Raquel F. ; Scarano, Wellerson R.

• Tipo de documento: Artigo Científico
• Fonte: ENVIRONMENTAL TOXICOLOGY; v. 31, n. 10, p. 1185-1195, OCT 2016.
• Citações Web of Science: 5

Resumo

In the present study, it was evaluated the susceptibility of prostatic lesions in male adult rats exposed to Di-N-butyl-phthalate during fetal and lactational periods and submitted to MNU plus testosterone carcinogenesis protocol. Pregnant females were distributed into four experimental groups: CN (negative control); CMNU (MNU control); TDBP100 (100 mg/kg of DBP); TDBP500 (500 mg/kg of DBP). Females from the TDBP groups received DBP, by gavage, from gestation day 15 (GD15) to postnatal day 21 (DPN21), while C animals received the vehicle (corn oil). CMNU, TDBP100, and TDBP500 groups received a single intraperitoneal injection of MNU (50 mg/kg) on the sixth postnatal week. After that, testosterone cypionate was administered subcutaneously two times a week (2 mg/kg) for 24 weeks. The animals were euthanized on PND220. Distal segment fragments of the ventral (VP) and dorsolateral prostate (DLP) were fixed and processed for histopathological analysis. Protein extracts from ventral prostate were obtained, and western blotting was performed to AR, ER, MAPK (ERK1/2), and pan-AKT. Stereological analysis showed an increase in the epithelial compartment in TDBP100 and TDBP500 compared to CN. In general, there was increase in the incidence of inflammation and metaplasia/dysplasia in the DBP-treated groups, mainly in DLP, compared to CN and CMNU. Proliferation index was significant higher in TDBP500 and PIN (prostatic intraepithelial neoplasia) was more frequent in this group compared to CMNU. Western blot assays showed an increase in the expressions of AR and MAPK (ERK1/2) in the TDBP100 compared to CN, and ER and AKT expressions were higher in the TDBP500 group compared do CN. These results showed that different doses of DBP during prostate organogenesis in Wistar rats could increase the incidence of premalignant lesions in initiated rats inducing distinct biological responses in the adulthood. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1185-1195, 2016. (AU)

• Processo FAPESP: 11/06633-0 - Expressão das proteínas MAPK (ERK1/2) e AKT e índices de proliferação e morte celular na próstata de ratos expostos ao Di-n-Butil-Ftalato (DBP) desde o período fetal, iniciados pela N-Metil-N-Nitrosuréia (MNU)
• Beneficiário: Andre Rebelo Peixoto
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 10/01143-1 - Potencial carcinogênico do agente plastificante Di-n-Butil-Ftalato (DBP) sobre a próstata de ratos adultos expostos desde o período fetal, iniciados pela N-Metil-N-Nitrosuréia (MNU)
• Beneficiário: Wellerson Rodrigo Scarano
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/10105-9 - Expressão de receptores hormonais (AR e ERa) e de IGF1-R na próstata de ratos expostos ao Di-n-Butil-Ftalato (DBP) desde o período fetal, iniciados pela N-Metil-N-Nitrosuréia (MNU).
• Beneficiário: Talita de Mello Santos
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica