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Background/aim: This study aimed to investigate the influence of Western diet on mammary cancer in Wistar female rats, focusing on systemic responses and tumor development., Materials and Methods: Twenty-eight Wistar female rats were acclimatized and divided into four experimental groups (n=7 each): Western diet (WD), Western diet with N-methyl-N-nitrosourea (MNU) administration (WD+MNU), standard diet (CTR), and standard diet with MNU administration (CTR+MNU). MNU was administered intraperitoneally at 50 mg/kg at seven weeks of age to induce mammary cancer. The 20-week experiment involved monitoring animal weight, food and water intake. At the end of the study, rats were euthanized, and blood samples and organs were collected for hematological and plasma biochemical analysis, oxidative stress, and histo-pathological and immunobiological evaluations of the tumors., Results: No significant differences were found in body weight, composition, or organ weights, but the WD group showed reduced food and water intake and lower cholesterol levels. Leptin and adiponectin levels were higher in the WD+MNU group, suggestive of changes in appetite regulation. Histopathological analysis showed malignant tumors in both MNU-induced groups. However, WD groups had fewer tumors compared to the CTR+MNU group., Conclusion: WD led to higher feed efficiency and increased visceral adipose tissue but decreased systemic cholesterol and triglyceride levels. While this diet resulted in lower tumor incidence, the volume and weight of the tumors were higher. Additionally, the WD decreased ERα and progesterone receptor immunoexpression, while Ki-67 immunoexpression was elevated., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Chemically-induced mammary tumors in rats by the carcinogens 1-methyl-1-nitrosourea- (MNU) and 7,12-dimethylbenz[a]anthracene (DMBA) are the most widely used models for studies related with human breast cancer. This study aimed to evaluate the immunoexpression of the prognostic factors estrogen receptor α (ERα), progesterone receptor (PR) and Ki-67, in MNU and DMBA-induced rat mammary tumors, in order to know the model that best suits to woman breast cancer. Twenty-eight MNU-induced and 16 DMBA-induced mammary tumors in virgin female Sprague-Dawley rats were analyzed. The expression of the prognostic markers ERα, PR and Ki-67 proliferation index (Ki-67 PI) was assessed by immunohistochemistry. Mitotic activity index (MAI) was also evaluated. More than one histological pattern was identified in each mammary tumor. Carcinomas constituted the lesions most frequently induced by both carcinogens: 33 MNU-induced carcinomas and 23 DMBA-induced carcinomas. All MNU and DMBA-induced mammary carcinomas were ER + /PR + , with a higher expression of ERα when compared with PR. Tumors' weight, the expression of ERα, PR, Ki-67 PI and MAI were higher in MNU-induced mammary carcinomas when compared with the DMBA-induced ones. Statistically significant differences between groups were observed for ERα, PR and MAI (p<0.05). The higher KI-67 PI and MAI in MNU-induced mammary carcinomas are suggestive of a higher aggressiveness of these carcinomas when compared with the DMBA-induced ones, and consequently a worse response to the therapy and a worse prognosis. In this way, the use of the rat model of MNU-induced mammary tumors is advised in experimental protocols aiming to study more aggressive mammary tumors within the group of double-positive mammary tumors (ER + /PR + )., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Mammary cancer is one of the most common cancers, victimizing more than half a million of women worldwide every year. Despite all the studies in this field, the current therapeutic approaches are not effective and have several devastating effects for patients. In this way, the need to better understand the mammary cancer biopathology and find effective therapies led to the development of several rodent models over years. With this review, the authors intended to provide the readers with an overview of the rat models used to study mammary carcinogenesis, with a special emphasis on chemically-induced models., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/aim: The effects of mast cells on carcinogenesis is not yet fully understood. This work aimed to disclose the role of mast cells in mammary carcinogenesis in a rat model., Materials and Methods: Mammary tumors were induced by the administration of N-methyl-N-nitrosourea (MNU) in three groups of rats. Animals from one group were treated with ketotifen immediately after MNU administration, and animals from another only received ketotifen after the development of the first mammary tumor. The biochemical profile was determined. Mammary tumors were evaluated by histopathology and immunohistochemistry., Results: Animals from ketotifen-treated groups developed fewer mammary tumors, higher number of mammary lesions and had lower histamine levels when compared to non-treated animals. Animals treated with ketotifen immediately after MNU exhibited the lowest proliferative and apoptotic indexes., Conclusion: The mainly positive effect of the inhibition of mast cell degranulation seems to be the reduction of tumor proliferation when the mast cell degranulation was inhibited before tumor development., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Although the rat model of mammary tumors chemically induced by N-methyl-N-nitrosourea (MNU) has been frequently used by several research teams, there is a lack of ultrastructural studies in this field. The main aim of this work was to perform an ultrastructural characterization of MNU-induced mammary tumors in female rats. Some alterations previously reported in human mammary tumors, such as nucleus size and shape, accumulation of heterochromatin in the perinuclear region, and interdigitating cytoplasmic processes between cancer cells were also observed in MNU-induced mammary tumors. Although a low number of samples were analyzed by transmission electron microscopy in the present study, we consider that it may contribute to a better understanding of MNU-induced mammary carcinogenesis in a rat model. The ultrastructural characteristics of the two most frequently diagnosed mammary carcinomas described in the present work can be useful to differentiate them from other histological patterns. In addition, the loss of cytoplasm in neoplastic cells and formation of vacuoles were described.

Background/aim: In this study, we evaluated the dimensions and volume of rat mammary tumors and the association of these variables with tumor invasiveness., Materials and Methods: Tumors were measured by caliper and ultrasonography. Volume was determined by water displacement and by application of four formulas using tumor length (L), width (W) and depth (D) or tumor weight., Results: Results confirmed the data obtained in our previous work, where we verified that mammary tumors grow as oblate spheroids., Conclusion: The determination of mammary tumor volume by applying the formula V=(4/3)×π×(L/2)×(L/2)×(D/2) is the best way to evaluate tumor volume in vivo. Beyond volume evaluation by water displacement, the determination on the basis of tumor weight is the most accurate way to evaluate tumor volume after animal sacrifice or tumor excision. According to our results, it is not possible to predict if a tumor is invasive or non-invasive by its dimensions, volume or weight. Future work in chemically-induced mammary cancer should use ultrasonography and water displacement or tumor weight to determine tumor volume in vivo and after animal sacrifice or tumor excision, respectively., (Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: Estrogen receptor α (ERα) and Ki-67 are strong prognostic and predictive markers in woman breast cancer. This study aimed to evaluate the immunoexpression of prognostic factor markers ERα, Ki-67 proliferation index (Ki-67 PI) and the mitotic activity index (MAI) in mammary tumors induced by 1-methyl-1-nitrosourea (MNU) in female Sprague-Dawley rats submitted to lifelong exercise training., Materials and Methods: Thirty female rats were injected with MNU and randomly divided into two groups: sedentary and exercised., Results: All neoplasms from both groups were ERα-positive with an H-score ≥20. Statistically significant differences were not found in the ERα H-score, Ki-67 PI and MAI between groups. The absolute value of ERα H-score was higher in the exercised group, while the Ki-67 PI and MAI were higher in the sedentary group., Conclusion: Tumors from the exercised group were less proliferative and more differentiated, suggesting that long-term exercise training had positive effects on mammary carcinogenesis., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The administration of chemical carcinogens is one of the most commonly used methods to induce tumors in several organs in laboratory animals in order to study oncologic diseases of humans. The carcinogen agent N-methyl-N-nitrosourea (MNU) is the oldest member of the nitroso compounds that has the ability to alkylate DNA. MNU is classified as a complete, potent, and direct alkylating compound. Depending on the animals' species and strain, dose, route, and age at the administration, MNU may induce tumors' development in several organs. The aim of this manuscript was to review MNU as a carcinogenic agent, taking into account that this carcinogen agent has been frequently used in experimental protocols to study the carcinogenesis in several tissues, namely breast, ovary, uterus, prostate, liver, spleen, kidney, stomach, small intestine, colon, hematopoietic system, lung, skin, retina, and urinary bladder. In this paper, we also reviewed the experimental conditions to the chemical induction of tumors in different organs with this carcinogen agent, with a special emphasis in the mammary carcinogenesis.