N-Methyl-N-nitrosourea as a mammary carcinogenic agent

Abstract

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.

Mast Cells in Mammary Carcinogenesis: Host or Tumor Supporters?

“…However, this mast cell stabilizer drug is a weak inhibitor of human mast cells and is not used in humans (27). Mammary tumors chemically induced by the carcinogen MNU in female Sprague-Dawley rats have long been used for the study of mammary carcinogenesis (28). In the present study, mammary tumors were successfully induced 8 weeks after MNU administration in animals exposed to this carcinogen.…”

“…However, conversely to the 100% incidence previously observed in work performed by our research team using the same model, in the present work a maximum incidence of 89% was reached. This difference is probably related to the duration of the experimental protocol: in the first study, the animals were sacrificed 35 weeks after MNU administration, while in the present one, they were sacrificed 18 weeks after MNU administration (28,29). Although the number of mammary tumors at the end of the experiment was slightly lower in animals from group III that only received the ketotifen after the development of the first mammary tumor, the mean number of mammary tumors per animal was lower in group II, i.e.…”

Anti-Helicobacter Pylori Activity and Immunostimulatory Effect of Oligosaccharide Isolated From Averrhoa Carambola L.

“…S3W was highly potent against H. pylori proliferation and its mechanism can be attributed to its anti-radical and immunostimulatory properties. Macrophages exposed to oxidants and MNU, a carcinogen most notably to cause adenocarcinoma of the stomach [42], were protected by S3W from undergoing damage significantly. Enhancement of phagocyte function is an established therapeutic application against microbial infection and cancer.…”

Maternal Resveratrol Treatment Reduces the Risk of Mammary Carcinogenesis in Female Offspring Prenatally Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin

“…The bcl-2/bax ratio intrinsically controls the relative susceptibility of target cells to induce apoptosis [49,50]. MNU carcinogen is a direct methylating agent that reacts with key cellular macromolecules, including DNA, causing relatively high levels of O6-methylguanine adducts, which results in a predominant DNA lesion and can potentially initiate cancer in susceptible target tissue, including the mammary gland [51]. Thus, MNU has been used as a potent carcinogen in chemically induced rat mammary carcinogenesis models using prepubertal and pubertal female rats [7,51], exerting acute cytotoxicity on mammary epithelial cells by inducing DNA damage and/or cell death [40].…”