Absence of uterine tumours in CD-1 mice treated neonatally with subcutaneous tamoxifen or 4-hydroxyoestradiol. 2007

Nihal Razvi, and Peter Greaves, and Jerry Styles, and Richard Edwards, and Ian N H White
MRC Molecular Endocrinology Group, Department of Cancer Studies and Molecular Medicine, University of Leicester, Robert Kilpatrick Building, Leicester LE2 7LX, UK.

The effects of subcutaneous dosing of neonatal CD-1 mice with tamoxifen on days 1-5 after birth at doses of 0, 5, 10, 25 or 50 microg/pup or with 4-hydroxyoestradiol at 2 microg/pup have been investigated. Animals were culled at 1.5, 3, 6, 12 and 18 months after dosing and changes in uterine and ovarian pathology examined. Results showed both compounds to result in uterine hypoplasia relative to controls. At 18 months after dosing in the uterus, there was a fairly marked atrophy of the muscle layer, mild to moderate glandular hyperplasia of the endometrium even though these irregularly shaped glands did not penetrate through the myometrium and no adenocarcinomas were detected. At 18 months after dosing, oviducts showed mild focal adenomatous changes characterized by penetration epithelial hyperplasia, changes similar to those previously reported as 'diverticulosis and salpingitis isthmica nodosa' following diethylstilbestrol treatment of mice. At this time, both tamoxifen and 4-hydroxyoestradiol also affected the ovaries which showed a paucity of follicles and no corpora lutea, suggesting that there had been disruption to the oestrus cycle, particularly with tamoxifen at the highest dose where the ovaries of mice contained no developing follicles. At 18 months, control mice were cycling normally. Results failed to substantiate that tamoxifen and 4-hydroxyoestradiol are uterine carcinogens in this neonatal mouse model.

UI MeSH Term Description Entries
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010053 Ovary The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE. Ovaries
D002393 Estrogens, Catechol 2- or 4-Hydroxyestrogens. Substances that are physiologically active in mammals, especially in the control of gonadotropin secretion. Physiological activity can be ascribed to either an estrogenic action or interaction with the catecholaminergic system. Catechol Estrogens,Catecholestrogens
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004717 Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the MENSTRUAL CYCLE and PREGNANCY. The endometrium undergoes cyclic changes that characterize MENSTRUATION. After successful FERTILIZATION, it serves to sustain the developing embryo. Endometria
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
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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