Ultrastructural and biochemical response of rat mammary epithelial cells to vinblastine sulfate.

Effects of vinblastine on cell ultrastructure and synthesis and secretion of proteins were studied in rat mammary epithelial cells. At high concentrations, this alkaloid induced drastic structural alterations in secretory epithelia both in vivo and in vitro including cytoplasmic swelling, depolarization and vesiculation of rough endoplasmic reticulum. At lower concentrations, vinblastine induced structural changes similar to those induced by colchicine using the same system. Secretory vesicles accumulated in the cytoplasm, there was hypertrophy of the rough endoplasmic reticulum and portions of the rough endoplasmic reticulum became vesiculated and engorged with electron-dense material. Microtubules were absent but paracrystalline structures were frequently observed associated with Golgi components. In vitro biochemical studies with dissociated alveoli demonstrated that vinblastine inhibited both the synthesis and secretion of protein. Thus the ultrastructural effects of vinblastine in mammary epithelia are similar to those induced by other alkaloids that affect microtubule integrity, but in contrast to colchicine, this alkaloid has a pronounced effect on protein synthesis.