Lipidosis induced in rat uteri by high doses of tamoxifen.

The anti-estrogenic drug tamoxifen is an amphiphilic cationic compound and might therefore be expected to interfere with intralysosomal catabolism of polar lipids as has been previously reported with several other amphiphilic cationic drugs. The purpose of this study was to investigate whether there is lipidosis induction in the uterus. High oral doses of tamoxifen (100 mg/kg) were administered to 9 adult rats for 6-14 weeks. Their uteri were examined by light and electron microscopy. Lipidosis-like alterations were seen in the glandular epithelia and in the myometrium. The luminal epithelium was most severely affected. The highest degree of intraepithelial change was already observed after a short-term treatment (6 weeks). The results support the previously proposed concept of a relationship between the amphiphilic cationic character of a compound and its ability to cause intralysosomal storage of polar lipids after a high dosage treatment of these drugs in animals.