Diuron-induced rat bladder epithelial cytotoxicity

Mitscheli S. Da rocha, Lora L Arnold, Karen L. Pennington, David Muirhead, Puttappa R. Dodmane, Muhammad M. Anwar, Michael Battalora, João Lauro V De camargo, Samuel Monroe Cohen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Diuron, 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.

Original languageEnglish (US)
Pages (from-to)281-288
Number of pages8
JournalToxicological Sciences
Volume130
Issue number2
DOIs
StatePublished - Dec 1 2012

Fingerprint

Diuron
Cytotoxicity
Rats
Urinary Bladder
Electrons
Scanning
Hyperplasia
Swelling
Deoxyuridine
Cell proliferation
Herbicides
Transmission Electron Microscopy
Organelles
Labeling
Piles
Optical microscopy
Urea
Wistar Rats
Microscopy
Cytoplasm

Keywords

  • Cytotoxicity
  • Diuron
  • Electron microscopy
  • Morphology
  • Proliferation
  • Urinary bladder

ASJC Scopus subject areas

  • Toxicology

Cite this

Da rocha, M. S., Arnold, L. L., Pennington, K. L., Muirhead, D., Dodmane, P. R., Anwar, M. M., ... Cohen, S. M. (2012). Diuron-induced rat bladder epithelial cytotoxicity. Toxicological Sciences, 130(2), 281-288. https://doi.org/10.1093/toxsci/kfs256

Diuron-induced rat bladder epithelial cytotoxicity. / Da rocha, Mitscheli S.; Arnold, Lora L; Pennington, Karen L.; Muirhead, David; Dodmane, Puttappa R.; Anwar, Muhammad M.; Battalora, Michael; De camargo, João Lauro V; Cohen, Samuel Monroe.

In: Toxicological Sciences, Vol. 130, No. 2, 01.12.2012, p. 281-288.

Research output: Contribution to journalArticle

Da rocha, MS, Arnold, LL, Pennington, KL, Muirhead, D, Dodmane, PR, Anwar, MM, Battalora, M, De camargo, JLV & Cohen, SM 2012, 'Diuron-induced rat bladder epithelial cytotoxicity', Toxicological Sciences, vol. 130, no. 2, pp. 281-288. https://doi.org/10.1093/toxsci/kfs256
Da rocha MS, Arnold LL, Pennington KL, Muirhead D, Dodmane PR, Anwar MM et al. Diuron-induced rat bladder epithelial cytotoxicity. Toxicological Sciences. 2012 Dec 1;130(2):281-288. https://doi.org/10.1093/toxsci/kfs256
Da rocha, Mitscheli S. ; Arnold, Lora L ; Pennington, Karen L. ; Muirhead, David ; Dodmane, Puttappa R. ; Anwar, Muhammad M. ; Battalora, Michael ; De camargo, João Lauro V ; Cohen, Samuel Monroe. / Diuron-induced rat bladder epithelial cytotoxicity. In: Toxicological Sciences. 2012 ; Vol. 130, No. 2. pp. 281-288.
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