Histopathology of mammary tumours in female rats treated with 1-methyl-1-nitrosourea.
ABSTRACT To induce, evaluate and classify advanced stages of mammary gland tumours induced by MNU.
Female Sprague-Dawley rats were injected intraperitoneally with 1-methyl-1-nitrosourea (MNU; 50 mg.kg-1) on the day 33, 40, 47, 54 and 61 of age in the first experiment and on 50th and 113th day in the second experiment. On the 117th day (first experiment) and on the 153rd day of age (second experiment) the rats were sacrificed by decapitation and their mammary glands were evaluated both macroscopically and microscopically for the presence of grossly detectable mammary tumours. Mammary tumours were classified according to Russo et al. (1990).
The final incidence of palpable carcinomas was ranging from 60 % to 76 %. All microscopically evaluated tumours were malignant. Among the total number of lesions classified the percentage of invasive tumours ranged from 35 % to 44 %. No metastases were observed in other organs in MNU treated animals.
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ABSTRACT: Retinoids are natural and synthetic compounds related to retinoic acid that act through interaction with two basic types of nuclear receptors: retinoic acid receptors (RARalpha, RARbeta and RARgamma) and retinoid X receptors (RXRalpha, RXRbeta and RXRgamma) as ligand-activated, DNA-binding, transacting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes. Function of retinoids in organisms affecting broad spectrum of various biochemical and molecular biology reactions is unimaginable without fully functional nuclear receptors--retinoid inducible transcription factors. Retinoic acids exert tumour-suppressive activity due to their antiproliferative and apoptosis-inducing effects. A number of novel retinoids and rexinoids acting through cognate nuclear receptors have been tested both in vitro and in vivo, using cell culture or animal models for breast cancer. This article briefly summarizes the role and properties of nuclear retinoid/rexinoid receptors as well as selected effects of retinoic acids or selected synthetic retinoids and rexinoids with respect to their potential use in chemoprevention of breast cancer.Central European journal of public health 04/2007; 15(1):3-6.
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ABSTRACT: Sodium weighted images can indicate sodium signal intensities from different features in the tumor before and 24 hours following administration of Taxotere. To evaluate the association of in vivo intracellular sodium magnetic resonance image intensities with immuno-biomarkers and histopathological features to monitor the early tumor response to Taxotere chemotherapy in Methyl-Nitroso-Urea induced rat xenograft breast tumors. Methyl-Nitroso-Urea (MNU) induced rat xenograft breast tumors were imaged for sodium MRI and compared with tumor histology, immunostaining after 24 hours chemotherapy. Sodium MRI signal intensities represented sodium concentrations. Excised tumor histological sections showed different in vitro histological end points i.e. single strand DNA content of cell nuclei during cell cycle (G1/S-G2/M), distinct S or M histograms (Feulgen labeling to nuclear DNA content by CAS 200), mitotic figures and apoptosis at different locations of breast tumors. Necrosis and cystic fluid appeared gray on intracellular (IC) sodium images while apoptosis rich regions appeared brighter on IC sodium images. After 24 hours Taxotere-treated tumors showed lower 'IC/EC ratio' of viable cells (65-76%) with higher mitotic index; apoptotic tumor cells at high risk due to cytotoxicity (>70% with high apoptotic index); reduced proliferation index (270 vs 120 per high power field) associated with enhanced IC sodium in vivo MR image intensities and decreased tumor size (3%; p < 0.001; n = 16) than that of pre-treated tumors. IC-Na MR signal intensities possibly indicated Taxotere chemosensitivity response in vivo associated with apoptosis and different pre-malignant features within 24 hours of exposure of cancer cells to anti-neoplastic Taxotere drug. Sodium MRI imaging may be used as in vivo rapid drug monitoring method to evaluate Taxotere chemosensitivity response associated with neoplasia, apoptosis and tumor histology features.Cancer Cell International 09/2005; 5:26. · 2.09 Impact Factor
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ABSTRACT: The incidence of breast cancer is continuously increasing worldwide. This increasing trend is attributed partly to the fact that a considerable number of cases are related to environmental factors and partly to the little information available on the early changes that occur during mammary gland carcinogenesis. To characterize some of these early cellular changes, breast cancer was induced in female rats using a single intragastric dose of the environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA; 80 mg/kg body weight). Mammary gland tissues of control and DMBA-treated rats were processed for routine histopathological examination and immunohistochemical analysis using an antibody specific for the proliferating cell nuclear antigen (PCNA). Microscopic examination of all mammary glands of DMBA-treated rats revealed a wide range of preneoplastic stages in addition to the well-characterized benign and malignant tumors that developed. The first stage was characterized by slightly dilated terminal ducts with accumulation of dead cells. This was designated the stage of cell death. Then, stages of hyperplasia, dysplasia, and carcinoma in situ followed. Immunohistochemical localization of PCNA in these preneoplastic lesions revealed an initial decrease followed by a gradual increase in the labeling index of PCNA. In conclusion, the DMBA-treated rats provide a useful model to dissect the early changes that occur during the multistep process of mammary gland carcinogenesis.Annals of the New York Academy of Sciences 10/2008; 1138:121-31. · 4.38 Impact Factor