Effects of B-retinyl acetate on human breast epithelium in explant culture.
Explants of human breast (obtained aseptically from ten women ages 18-37) were examined and the vitamin A compound B-retinyl acetate was tested (at 3 X 10(-5) and 3 X 10(-6) M) for its effects on the fine structure and growth of the epithelium. In the absence of B-retinyl acetate, cells growing out from the explant (outgrowth cells) underwent squamous metaplasia, began to accumulate many intermediate filaments (tonofilaments), and revealed large desmosomes after 2 weeks in culture. In the presence of either concentration of B-retinyl acetate, the epithelial cells were largely prevented from undergoing squamous metaplasia. The glandular epithelium inside the explant maintained a typical secretory appearance for 2 weeks in control cultures (without the retinoid) and then began to show increased numbers of lysosomes and a loss of secretory granules. These glandular epithelial cells did not undergo squamous metaplasia, but they contained increased numbers of intermediate filaments. In contrast, glandular epithelium cultured in either concentrations of B-retinyl acetate appeared secretory for as long 6 weeks in culture, and intermediate filaments were not obvious. Autoradiographs demonstrated that both concentrations of B-retinyl acetate inhibited cell division in the outgrowth epithelium and in the (internal) glandular epithelium. The ability of B-retinyl acetate to reverse squamous metaplasia in the outgrowth cells was also tested. Outgrowth cells reversed to a more normal ductlike appearance after 6 weeks culture in standard medium followed by only 1 week in 20 micrograms/ml B-retinyl acetate. After 7 weeks in standard medium and 1 week in 10 micrograms/ml B-retinyl acetate, the cells showed a partial reversal of the squamous metaplasia.
D000293:Adolescent; D000328:Adult; D001940:Breast / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D004261:DNA Replication; D004224:Diterpenes; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006801:Humans; D008854:Microscopy, Electron; D009924:Organ Culture Techniques; D000084562:Retinyl Esters; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology
D004224:Diterpenes; D000084562:Retinyl Esters; D014316:Tritium; D014801:Vitamin A; C009166:retinol acetate; D013936:Thymidine