Subsequent analysis regarding the early stage of the phenomenon revealed that neonatal DES exposure induced both acute and persistent changes in mitotic activity, organization, and dimensions of individual tissue compartments in the immature (prepubertal) uterus. To investigate the later stage of the phenomenon, we used mature animals that had been ovariectomized and then chronically stimulated with E2, and we observed endometrial hyperplasia/adenocarcinoma in the uteri exposed to DES neonatally, but not in the control uteri. More info
Those observations, when considered from the context of the two-step model for carcinogenesis, seemed to be consistent with the hypothesis that 1) neonatal DES treatment directly and permanently alters the developing hamster uterus (initiating event) such that 2) the uterus responds abnormally later in life to stimulation with E2 (promotion event).
Strong support for the two-stage hypothesis came from a study in which immature uteri from control and neonatally DES-treated donors were cross-transplanted and allowed to develop in the cheek pouches of control and neonatally DES-exposed hosts that had also been ovariecto-mized and then chronically stimulated with E2.