Carcinogenic potential of the plasticizer Di-n-butyl-phthalate (DBP) on the prostate of adult rats exposed from the fetal period, initiated by N-methyl-N-nitrosourea (MNU)

• Grant number: 10/01143-1
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2010
• End date: July 31, 2012
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Wellerson Rodrigo Scarano
• Grantee: Wellerson Rodrigo Scarano
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Luís Fernando Barbisan ; Raquel Fantin Domeniconi ; Sebastião Roberto Taboga ; Sérgio Luis Felisbino

Abstract

In view of the world problem related to the plastics degradation and its environmental dispersion and before our previous study which histopathological and biochemical changes in the prostate of animals exposed to DBP (Di-n-butyl-phthalate) in the perinatal period were observed, this study aims to evaluate the carcinogenic potential of DBP administered from the fetal period and after the initiation MNU, in a model of prostate carcinogenesis. Dams will be divided into 4 groups: 2 treated: n = 16/grupo (TDBP100 and TDBP500) and 2 controls: n = 8/grupo (CN and CMNU). TDBP100 group will be exposed to DBP (100 mg / kg) and TDBP500 to 500 mg/kg from 15GD (gestation day) to 21PND (postnatal day), while control animals receive the vehicle. After weaning, the males will be separated and treated groups and CMNU receive a single dose of MNU (50 mg / kg, ip) in the 6th. postnatal week. Half of the animals treated (n = 8/grupo) will continue to receive the DBP after weaning at weekly doses until the day of sacrifice (180. DPN), while others will be kept for the same period without treatment. On the day of sacrifice, the blood will be collected, the reproductive organs are weighed and fragments of the ventral and dorsolateral lobes of the prostate are processed for structural analysis; immunocytochemistry for AR (androgen receptor), P63 (prostatic stem cells), Ki 67, cleaved caspase 3 and ER± (estrogen receptor) will be release in the ventral lobe. Fragments of ventral prostate will be frozen and stored at -80 ° C and after proteins extraction, they will be designated for the Western blot method to evaluate the expression of AR and ER±, and in case of pre-malignant lesions and malignant: MAPK, AKT and IGF1-R. This study intends to continue the study recently published by our research group to consolidate my research line on endocrine disrupters and experimental carcinogenesis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

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.. 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. ENVIRONMENTAL TOXICOLOGY, v. 31, n. 10, p. 1185-1195, OCT 2016. (11/06633-0, 10/01143-1, 11/10105-9)