Cell types present in the mammary gland and their evolution were studied by labeling female rats with radioactive thymidine at various phases of the estrus cycle. The results suggest that the stem cells for mammary development are present in the terminal end buds and that they generate a lineage for lumenal cells and possibly a distinct one for myoepithelial cells. Growth and differentiation are controlled by both hormones and local factors.The mammary. gland is the site of very frequent cancers in humans as. well as in animals. The formation of these cancers appears to be influenced by the developmental changes occurring in the gland after birth: in female rats the inducibility of cancer by chemicals.is maximal at 50-60 days ofage, when the changes are at their peak; pregnancy, lactation, and hormone treatments affect the incidence of mammary cancer in women.and in animals. Therefore, a knowledge of the cell types present in the mammary gland and their evolution may be useful for understanding carcinogenesis.In the young rat the mammary gland consists of a system of branching ducts, which terminate with actively growing structures, the terminal end buds (TEB); the ducts.show branching (sometimes extensive) into ductules, also-called alveolar buds. Essentially only two cell types are clearly recognized in these structures: the epithelial cells that line the lumen of ducts and ductules and the myoepithelial cells that surround them. However, three types are recognized from nuclear morphology (1). In lactation the alveoli (which derive from ducts and ductules) are lined by functionally different cells, those producing milk, which also are surrounded by myoepithelial cells. The differentiation ofthe mammary gland is under the control ofmultiple hormones. Many observations show that estrogens. promote end-bud. development and duct elongation and that progesterone promotes duct enlargement and ductule formation and growth (2-7).We have taken advantage ofthe hormonal changes occurring during the normal estrus cycle of the mature virgin female rats to identify cell types with differential growth responses. The basic approach was to label the cells by an injection of [3H]dThd into the animal at defined phases of the estrus cycle and to detect the. DNA-synthesizing cells in histological slices by autoradiography (4-10). By allowing time periods ofvarious lengths between injection and removal of the gland for examination, pulse-chase experiments also were performed. These approaches identify several kinds of epithelial mammary cells and suggest a possible developmental pathway. The experiments were complemented by studies with various cell markers, which will be reported separately. MATERIALS AND METHODSForty-two female Sprague-Dawley rats were used, most as cycling adults (50-60 days of age) and some as immature animals (ca. 25 days). The estrus phases were determined by vaginal smears. Groups ofanimals were injected intraperitoneally with[3H]dThd (20 Ci/mmol; 1 Ci = 3.7 x 10W°becquerels), by using 0.5 mCi for a...

Diaphragm disease (DD) is a radiographically subtle cause of small bowel obstruction and is part of the spectrum of diseases associated with nonsteroidal anti-inflammatory drug injury. The neuromuscular and vascular hamartoma (NMVH) is a nonepithelial hamartomatous, submucosally based proliferation of mature submucosal elements capable of causing small bowel obstruction. The authors report two patients in whom the clinical setting and gross pathology are that of DD, but the histologic characterization is identical to that described for NMVH. It is probable that in some patients the two diseases overlap so that some patients readily fit the criteria for both entities.