Evaluation of Carcinogenic Potential of Diuron in a Rat Mammary Two-Stage Carcinogenesis Model

Abstract

This study aimed to evaluate the carcinogenic potential of the herbicide Diuron in a two-stage rat medium-term mammary carcinogenesis model initiated by 7,12-dimethylbenz(a)anthracene (DMBA). Female seven-week-old Sprague-Dawley (SD) rats were allocated to six groups: groups G1 to G4 received intragastrically (i.g.) a single 50 mg/kg dose of DMBA; groups G5 and G6 received single administration of canola oil (vehicle of DMBA). Groups G1 and G5 received a basal diet, and groups G2, G3, G4, and G6 were fed the basal diet with the addition of Diuron at 250, 1250, 2500, and 2500 ppm, respectively. After twenty-five weeks, the animals were euthanized and mammary tumors were histologically confirmed and quantified. Tumor samples were also processed for immunohistochemical evaluation of the expressions of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, estrogen receptor-a (ER-a), p63, bcl-2, and bak. Diuron treatment did not increase the incidence or multiplicity of mammary tumors (groups G2 to G4 versus Group G1). Also, exposure to Diuron did not alter tumor growth (cell proliferation and apoptosis indexes) or immunoreactivity to ER-a, p63 (myoephitelial marker), or bcl-2 and bak (apoptosis regulatory proteins). These findings indicate that Diuron does not have a promoting potential on mammary carcinogenesis in female SD rats initiated with DMBA.

Sexual neurosteroids and synaptic plasticity in the hippocampus

“…This finding is consistent with the findings of Grassi et al (2011). They found, however, that the potentiation after high frequency stimulation was markedly reduced in the presence of letrozole in males compared to that induced under control conditions.…”

Effects of Ginkgo biloba on chemically-induced mammary tumors in rats receiving tamoxifen

“…Proliferating cell nuclear antigen (PCNA) is a 36 kDa molecule that acts as a DNA polymerase co-factor during chromosome replication and is easily detected during S-phase of the cell cycle [29]. Therefore, PCNA is widely used as a reliable cell proliferation biomarker in experimental models of chemical carcinogenesis, including models of rat mammary carcinogenesis [24,29,30]. In the present study, the reduced PCNA LI% observed in TAM-treated rats can be explained by the ability of TAM to inhibit estrogen receptor (ER)-dependent cell proliferation in mammary tumors [31].…”

Assessment of female reproductive endpoints in Sprague–Dawley rats developmentally exposed to Diuron: potential ovary toxicity

“…1) and mammary glands removed and fixed for 24 hr in 10% phosphate‐buffered formalin. Samples of organs/tissues were processed in order to provide 5 µm‐thick paraffin sections for histology (hematoxylin–eosin]) and immunohistochemical analysis for proliferating cell nuclear antigen (PCNA), cleaved caspase‐3 and estrogen‐receptor‐alpha (ER‐α) (Grassi et al, 2011).…”