XENOESTROGENS ALTER MAMMARY-GLAND DIFFERENTIATION AND CELL-PROLIFERATION IN THE RAT

We investigated mammary glad differentiation and cell proliferation in rats after acute exposure to xenoestrogens. Pubertal female Sprague-D awley rats (six/groups) were treated for 1 week with diethylstilbestro l (DES), genistein, o,p'-DDT, Aroclor 1221, Aroclor 1254, 2,3,7,8-tetr achlorodibenzo-p-dioxin (TCDD), or the vehicle, sesame oil. Animals we re killed 18 hr after the last treatment. Analysis of mammary whole-mo unts revealed that exposure to DES, genistein and o,p'-DDT resulted in enhanced gland differentiation and increase epithelial cell prolifera tion as measured by proliferating cell nuclear antigen immunohistochem istry. TCDD treatment inhibited cell proliferation and gland developme nt. Aroclor 1221 and Aroclor 1254 treatments had slight but not statis tically significant effects on cell proliferation and mammary gland de velopment. We conclude that DES, genistein, and o,p'-DDT given to pube rtal rats act as morphogens; i.e., they increase cell proliferation, w hich promotes maturation of the undifferentiated terminal end buds to more differentiated lobular terminal ductal structures.