Neoplastic transformation and DNA damage of mouse mammary epithelial cells by N-methyl-N'-nitrosourea in organ culture. 1990

C R Delp, and J S Treves, and M R Banerjee
Tumor Biology Laboratory, School of Biological Sciences, University of Nebraska-Lincoln 68588-0342.

An appropriate in vitro system was used to study the effect of a direct-acting carcinogen on the transformation of mammary epithelial cells in the organ culture of the whole mammary gland in vitro. Studies were done to determine the ability of N-methyl-N'-nitrosourea (MNU) to transform the mammary cells in organ culture. Mouse mammary glands were treated with single or multiple doses of MNU during various periods of the culture. To assay for neoplastic transformation potential of MNU on mammary cells, mammary glands were dissociated and the cells were injected into the parenchyma-free inguinal mammary fat pad of syngeneic virgin female host mice. Palpable tumors were observed in injected glands of 23% of the mice after 3-4 months and an additional 31% showed serially transplantable hyperplastic alveolar nodules (HANs). Histopathologic examination of the tissues showed that the tumors were mammary adenocarcinoma. All tumors and hyperplasias were secondarily transplanted into syngeneic animals, resulting in tumors and hyperplasias of similar histopathology. In addition, DNA damage of the epithelial cells in organ culture caused by MNU was also measurable using the new nick translation assay. The most extensive DNA damage occurred when the glands were treated on day 4 and day 5 of the mammogenic culture period. These results demonstrate that the mouse mammary epithelial cells are susceptible to the carcinogenic action of the direct-acting carcinogen MNU and that the whole mammary gland-culture system offers an appropriate in vitro model for studying the mechanism of carcinogenesis induced by MNU.

UI MeSH Term Description Entries
D008321 Mammary Glands, Animal MAMMARY GLANDS in the non-human MAMMALS. Mammae,Udder,Animal Mammary Glands,Animal Mammary Gland,Mammary Gland, Animal,Udders
D008325 Mammary Neoplasms, Experimental Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS. Experimental Mammary Neoplasms,Neoplasms, Experimental Mammary,Experimental Mammary Neoplasm,Mammary Neoplasm, Experimental,Neoplasm, Experimental Mammary
D008770 Methylnitrosourea A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties. Nitrosomethylurea,N-Methyl-N-nitrosourea,NSC-23909,N Methyl N nitrosourea,NSC 23909,NSC23909
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D009924 Organ Culture Techniques A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1) Organ Culture,Culture Technique, Organ,Culture Techniques, Organ,Organ Culture Technique,Organ Cultures
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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