Potential effects of the herbicide Diuron on mammary and urinary bladder two-stage carcinogenesis in a female Swiss mouse model

Author(s)

de Moura, Nelci Antunes ^[1] ; Grassi, Tony Fernando ^[2] ; Marchesan Rodrigues, Maria Aparecida ^[2] ; Barbisan, Luis Fernando ^{[2, 1]}

Affiliation

^[1] UNESP Sao Paulo State Univ, Dept Morphol, Inst Biosci, BR-18618000 Botucatu, SP - Brazil

^[2] UNESP Sao Paulo State Univ, Dept Pathol, Fac Med, BR-18618000 Botucatu, SP - Brazil

• Document type: Journal article
• Source: ARCHIVES OF TOXICOLOGY; v. 84, n. 2, p. 165-173, FEB 2010.
• Web of Science Citations: 9

Abstract

The potential promoting effect of Diuron was investigated in a mouse model of mammary and urinary bladder carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Four-week old female Swiss mice were allocated to five groups: Groups G1-G3 received DMBA (5 x 1.5 mg/mouse) and BBN (8 x 7.5 mg/mouse) and G4 and G5 groups received only vehicles during the first 6 weeks. At week 7, G1 and G5 groups received basal diet and G2, G3 and G4 groups were fed a diet containing Diuron at 1,250, 2,500 and 2,500 ppm, respectively, during 13 weeks. At week 20, the animals were euthanized and the gross tumors were registered. Mammary glands and urinary bladder were processed for histopathological analysis. Samples from non-tumor areas were evaluated for cell proliferation by 5-bromodeoxyuridine labeling index (BrdU-LI%) and apoptosis. Dietary treatment with Diuron at 1,250 and 2,500 ppm significantly increased BrdU-LI% (P < 0.05) and the incidence of simple/nodular urothelial hyperplasia in the urinary bladder from DMBA/BBN-initiated groups (G2 and G3 vs. G1, P < 0.02) and in the non-initiated group (G4 vs. G5, P = 0.042). Two transitional cell carcinomas were observed in the group initiated and fed Diuron 2,500 ppm (G3). In contrast, in the mammary gland, Diuron feeding for 13 weeks did not significantly alter cell proliferation and apoptosis indexes or the incidence of hyperplastic lesions or neoplasms in the DMBA/BBN-initiated groups. These findings suggest that Diuron is a promoting agent to the urinary bladder but not to the mammary gland in female Swiss mice submitted to a medium-term two-stage carcinogenesis bioassay. (AU)

• FAPESP's process: 06/01330-0 - Mammary carcinogenesis in an experimental model of developmental (perinatal/juvenile/lactational) and adult exposure to the diuron herbicide [N-(3,4-dichlorophenyl)-N-N-dimethyl-urea] in female Sprague-Dawley
• Grantee: Tony Fernando Grassi
• Support Opportunities: Scholarships in Brazil - Doctorate