Effect of 5-bromo-2′-deoxyuridine on growth and differentiation of cultured embryonic retinal pigment cells

Publisher Website
Google Scholar
Abstract
Chicken embryo retinal pigment cells cultured for 2 weeks in 1 or 10 μm BrdU accumulate only 25% of the amount of melanin found in controls. Growth is inhibited by 10 μm BrdU but not by 1 μm BrdU. Cells cultured with BrdU had decreased tyrosinase activity and lost the typical epithelial appearance of controls. Equimolar concentrations of deoxythymidine did not prevent the inhibition of melanogenesis due to BrdU but did prevent the growth inhibition of the higher concentration of BrdU (10 μm). Tenfold higher concentrations of deoxythymidine prevented inhibition of epithelial differentiation and melanogenesis. Ultrastructurally, BrdU produced an absence of melanosomes and disruption of the lamellar array of rough endoplasmic reticulum. The perinuclear arrangement of microfilaments became irregular. The cell surface was radically affected as membranes were no longer ruffled and cell junctions disappeared. Melanogenesis is a complex form of differentiated function, involving synthesis of tyrosinase and control of its activity, macromolecular synthesis of the melanosome, and the subsequent synthesis of melanin within the melanosome. BrdU appears to inhibit melanogenesis through a coordinated and simultaneous interference with these processes, suggesting that there may be a “program” of gene activity for melanogenesis that is regulated as a unit.