Anti-oestrogenic and anti-tumour properties of prolonged tamoxifen therapy in C3H/OUJ mice.
The anti-oestrogenic and anti-tumour properties of a sustained-release preparation of tamoxifen were evaluated in female C3H/OUJ mice. Tamoxifen decreased uterine weight compared with controls in intact mice but caused an initial uterotrophic response for 2 months in ovariectomized mice. Prolonged tamoxifen therapy in ovariectomized mice resulted in a uterine weight no different from controls, but these uteri were eventually (at 6 months) refractory to oestradiol. Spontaneous mammary tumours were detected in female mice between 6 months and 1 year of age during continuous cycles of pregnancy and weaning. A similar tumour frequency occurred after one cycle of pregnancy and weaning initiated at 31/2 months. Prolonged tamoxifen, started at 31/2 or 41/2 months of age (following pregnancy/weaning), reduced the appearance of tumours. Similarly ovariectomy at 31/2 months prevented mammary tumorigenesis and prolonged tamoxifen could not increase tumour incidence consistently in ovariectomized mice. Although tamoxifen is oestrogenic in short-term tests the compound has the properties of an anti-oestrogen during prolonged administration.
Jordan
V C
VC
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
Lababidi
M K
MK
Mirecki
D M
DM
D000818:Animals; D003692:Delayed-Action Preparations; D004965:Estrogen Antagonists; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D009929:Organ Size / Q000187:drug effects; D013629:Tamoxifen / Q000008:administration & dosage* / Q000627:therapeutic use; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects
D003692:Delayed-Action Preparations; D004965:Estrogen Antagonists; D013629:Tamoxifen