Diuron-Induced Rat Bladder Epithelial Cytotoxicity

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorDa Rocha, Mitscheli S.
dc.creatorArnold, Lora L.
dc.creatorPennington, Karen L.
dc.creatorMuirhead, David
dc.creatorDodmane, Puttappa R.
dc.creatorAnwar, Muhammad M.
dc.creatorBattalora, Michael
dc.creatorCamargo, João Lauro Viana de
dc.creatorCohen, Samuel Monroe
dc.date2014-05-20T13:37:32Z
dc.date2016-10-25T16:54:12Z
dc.date2014-05-20T13:37:32Z
dc.date2016-10-25T16:54:12Z
dc.date2012-12-01
dc.date.accessioned2017-04-05T20:33:38Z
dc.date.available2017-04-05T20:33:38Z
dc.identifierToxicological Sciences. Oxford: Oxford Univ Press, v. 130, n. 2, p. 281-288, 2012.
dc.identifier1096-6080
dc.identifierhttp://hdl.handle.net/11449/13001
dc.identifierhttp://acervodigital.unesp.br/handle/11449/13001
dc.identifier10.1093/toxsci/kfs256
dc.identifierWOS:000311307600007
dc.identifierhttp://dx.doi.org/10.1093/toxsci/kfs256
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/860472
dc.descriptionDiuron, a substituted urea herbicide, is carcinogenic to the rat urinary bladder at high dietary levels (2500 ppm). To further elucidate the mode of action, this study aimed to determine the time course and sequence of bladder cytotoxic and proliferative changes induced by diuron treatment of male Wistar rats. Rats were randomized into two groups (control and 2500 ppm diuron) and treated for 28 days. Ten rats from each group were terminated on each of study days 1, 3, 7, or 28. Scanning electron micro scopy (SEM) showed urothelial cell swelling beginning on day 1, and by day 28, showed extensive necrosis, exfoliation and piling up of cells suggestive of hyperplasia. No difference in the bromo deoxyuridine labeling index was detected. In a second experiment, rats were randomized into control and diuron-treated groups and treated for 7 days or 8 weeks. After 7 days, transmission electron microscopy showed cell degenerative changes and distention of the cytoplasm, organelles, and nuclei characteristic of cytolysis. This resulted in protrusion of the superficial cells into the lumen, corresponding to the cell swelling observed previously by SEM. After 8 weeks, bladders in the diuron-treated group showed an increased incidence of simple hyperplasia by light microscopy (6/10, p < 0.05) compared with controls (0/10) and a significantly different SEM classification. In summary, our results support the hypothesis that urothelial cytotoxicity followed by regenerative cell proliferation are the sequential key events that occur with high-dose diuron exposure in rats.
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.languageeng
dc.publisherOxford University Press
dc.relationToxicological Sciences
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectDiuron
dc.subjecturinary bladder
dc.subjectcytotoxicity
dc.subjectproliferation
dc.subjectmorphology
dc.subjectelectron microscopy
dc.titleDiuron-Induced Rat Bladder Epithelial Cytotoxicity
dc.typeOtro


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