Gene expression profiling in the urothelium of male Wistar rats exposed to the herbicide Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea)

• Grant number: 09/02754-7
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2009
• End date: May 31, 2011
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: João Lauro Viana de Camargo
• Grantee: João Lauro Viana de Camargo
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• City of the host institution: Botucatu

Abstract

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide widely used on agricultural crops such as soy, cotton and sugar cane. Experimental evidences indicate that a high (2500ppm) dietary concentration of the Diuron exerts carcinogenic activity on the urinary bladder and renal pelvis mucosa of male Wistar rats (USEPA, 2002). Therefore, Diuron has been classified as "probably carcinogenic to human" (USEPA, 2004). A previous study of our group indicated that dietary 2500ppm Diuron is associated with urothelial necrosis and continuous regenerative cell proliferation that leads to urothelial hyperplasia. This could establish an unstable urothelium, prone to neoplasia development. There are no available information regarding the molecular mechanism of toxicity and carcinogenic activity of Diuron on the rat urinary bladder. The present study aims to evaluate the dose-response influence of Diuron on the urothelium of male Wistar rats and eventually to establish a NOAEL for its adverse effects. Male Wistar rats will be exposed to Diuron at 0, 60, 500, 1250 and 2500 ppm in diet during 20 weeks. After euthanasia, RNA will be extracted from bladder epithelial cells. The gene expression profile and the pathways analysis will be evaluated using cDNA microarray by Shadia Muhammad Ihlaseh, a PhD student (Fapesp 08/5644-1) at the National Health and Environmental Effects Research Laboratory, U. S. Environmental Protection Agency (USEPA), Research Triangle Park, NC, USA, under the supervision of Dr. Douglas Wolf. (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)

IHLASEH-CATALANO, SHADIA M.; BAILEY, KATHRYN A.; CARDOSO, ANA PAULA F.; REN, HONGZU; FRY, REBECCA C.; DE CAMARGO, JOAO LAURO V.; WOLF, DOUGLAS C.. Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron. Toxicology, v. 325, p. 21-30, NOV 5 2014. (06/60506-1, 09/02754-7)

DA ROCHA, MITSCHELI SANCHES; ARNOLD, LORA L.; COTRIM SARTOR DE OLIVEIRA, MARIA LUIZA; IHLASEH CATALANO, SHADIA M.; FERRAGUT CARDOSO, ANA PAULA; PONTES, MERIELEN G. N.; FERRUCIO, BIANCA; DODMANE, PUTTAPPA R.; COHEN, SAMUEL M.; DE CAMARGO, JOAO LAURO V.. Diuron-induced rat urinary bladder carcinogenesis: Mode of action and human relevance evaluations using the International Programme on Chemical Safety framework. CRITICAL REVIEWS IN TOXICOLOGY, v. 44, n. 5, p. 393-406, MAY 2014. (06/60506-1, 09/02754-7)

IHLASEH, SHADIA M.; BAILEY, KATHRYN A.; HESTER, SUSAN D.; JONES, CARLTON; REN, HONGZU; CARDOSO, ANA PAULA F.; OLIVEIRA, MARIA LUIZA C. S.; WOLF, DOUGLAS C.; DE CAMARGO, JOAO LAURO V.. Transcriptional Profile of Diuron-Induced Toxicity on the Urinary Bladder of Male Wistar Rats to Inform Mode of Action. TOXICOLOGICAL SCIENCES, v. 122, n. 2, p. 330-338, AUG 2011. (06/60506-1, 09/02754-7)