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Effects of neonatal dosing of SERMs on CD1 mouse uterine gene expression at 3 months

ABSTRACT: Tamoxifen, a selective estrogen receptor modulator (SERM), is an effective treatment for breast cancers. In the CD-1 mouse model, neonatal oral dosing with tamoxifen leads to the development of adenomyosis. Both 4-hydroxyestradiol and tamoxifen can form DNA-reactive metabolites and may be involved in carcinogenesis of the uterus. After comparing the uterotrophic response of several SERMs the maximal uterotrophic doses of estradiol (100mg/kg) 4-hydroxyestradiol (385mg/kg) and tamoxifen (250mg/kg) were determined. Maximal uterotrophic doses were given orally to newborn CD-1 mice on days 1 – 4 after birth and gene and pathological changes examined in the uterus at 3 months after dosing. ERKOa knockout mice were dosed orally with tamoxifen (1mg/Kg) on days 1 – 4 after birth and uterine gene expression compared with CD-1 mice. Dosing groups: Estradiol (E2): 100mg/Kg 4-hydroxyestradiol (4OHE2): 385mg/Kg Tamoxifen : 250mg/Kg ERKO mice dosed with tamoxifen (1mg/Kg) 4 dosed animals and 4 controls for each treatment group. Uteri removed at 3 months after dosing and total RNA extracted. Controls were pooled. RNA labelling, hybridisation and analysis of fluorescence was carried out as described by Turton et al (2001). Cy3/Cy5 dye swap labelling was carried out on samples from each animal. Reference: Turton NJ et. al. (Oncogene (2001) 20, 1300-1306

ORGANISM(S): Mus musculus  

SUBMITTER: Jerry A Styles  

PROVIDER: E-GEOD-3625 | ArrayExpress | 2010-06-30



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