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Gene expression Glipican 3 (Gpc3) in the bladder urothelium of rats exposed to diuron (3 - (3,4-dichlorophenyl) -1,1-dimethylurea) for 7 days and 20 weeks

Grant number: 11/21701-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2012
Effective date (End): December 31, 2012
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal researcher:João Lauro Viana de Camargo
Grantee:Lígia Maria Micai Gomide
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The diuron (3 - (3,4-dichlorophenyl) -1,1-dimethylurea) is a substituted urea herbicide widely used on sugarcane, cotton and soybeans crops. This agent has been classified by the United States Environmental Protection Agency (USEPA, 2004) as "probably carcinogenic to humans " because it induced tumors in the bladder and renal pelvis of rats, and breast and skin of mice exposed by ration to 2500 ppm of product for two years (USEPA, 2002). A previous study from our group demonstrated dose-response relationship in gene expression profile associated with severe necrosis focus of the bladder urothelium and increased incidence of simple hyperplasia in male Wistar rats treated with different concentrations of diuron for 20 weeks. To verify how the molecular alterations occurring early, rats were fed for 7 days on rations containing diuron at 0, 125, 500 or 2500 ppm. Among other observations, there were ultrastructural alterations of the mucosa and compromised molecular pathways associated with cell-cell interactions and maintenance of tissue organization. Particularly, the gene Glipican 3 (Gpc3), a surface proteoglycan involved in cell adhesion and apoptosis induction, decreases in expression after 7 days of exposure to 2500ppm of diuron, this change had been observed in the animals studied after 20 weeks of exposure the herbicide. The objective of this study is to assess the expression of Gpc3 gene in urinary bladder epithelial cells of male Wistar rats treated with different concentrations of diuron after 7 days and 20 weeks by quantitative real-time RT-PCR. This study aims to elucidate the role of Gpc3 in the urothelial toxicity by diuron and eventually identify a possible tumor suppressor gene in experimental chemical carcinogenesis in the urinary bladder, contributing information on the mode of action of this herbicide.