The cell proliferation stimulated by ovarian steroids may be an important determinant of cancer risk in hormonally responsive tissues, since there is an increased risk of genetic errors occurring during the process of cell division. DNA labeling index (DNA LI) was determined in mammary glands of female 35-day old (n=9) and adult cycling (3 to 8 months old, n=29) CD-1 mice, and was contrasted with the uterine lumenal and glandular epithelium labeling pattern in each animal. Vaginal smears were obtained to determine stage and regularity of the estrous cycle. Animals were injected (i.p.) with 5-bromo 2'-deoxyuridine (BrDU) at 50 mg/kg to label nuclei in S-phase, and 2 hours later the fourth mammary gland, a mid-section of the uterine horn and a piece of the duodenum were removed, fixed in ice-cold 4% paraformaldehyde overnight, dehydrated, embedded in paraffin and sectioned. Labeled nuclei were detected immunohistochemically with a rat anti-BrDU monoclonal antibody using the avidin biotin peroxidase method. DNA LI was expressed as the percent of labeled epithelial nuclei. Despite a variable pattern in the labeling of uterine epithelium in the 35-day old animals, all mammary glands examined displayed extensive labeling in the terminal end buds (TEBs) (Mean plus/minus SEM, 13.1 plus/minus 0.7). Ductal labeling was comparatively low (1.3 plus/minus 0.5) and did not appear to be related to the pattern of uterine epithelial labeling in these sub-adult mice. In contrast, mammary ductal labeling in adult animals was negatively correlated with the combined uterine lumenal and glandular epithelial DNA LI (p less that 0.05, r= -0.426). Animals (n=7) with the highest uterine DNA LI (40.2 to 70.8) had low mammary ductal DNA LI (less than 1.0), while the 4 animals with the highest mammary ductal DNA LI (4.4. to 10.9) had a uterine DNA LI of less than 0.5. Several animals with high mammary labeling had thin uteri, and were at the end of estrus or in metestrus. The inversely correlated patterns of epithelial DNA Li in uterus and mammary gland supports the concept that in adult animals the hormonal requirement for proliferation in the mammary gland is different from that of the uterus.
