5-bromodeoxyuridine may alter the differentiative program of the embryonic pancreas.

Abstract

The thymidine analog, 5-bromodeoxyuridine (BrdU), inhibits the differentiation of the acinar cells of the embryonic rat pancreas, while having little effect on the growth of the tissue. The BrdU-treated pancreas contains elevated alkaline phosphatase and carbonic anhydrase activities, and, unlike the normal pancreas, contains numerous extracellular fluid-filled vacuoles, surrounded by ductlike cells. Both alkaline phosphatase and carbonic anhydrase activities are located preferentially in the ductlike cells lining the vacuoles. The biochemical, morphological, and functional features of these epithelial cells are therefore characteristic of the normal pancreatic duct cell. Thus, in the exocrine pancreas, BrdU seems to alter the normal program of differentiation by favoring the formation of functional duct cells while inhibiting the differentiation of acinar cells.The thymidine analog, 5-bromodeoxyuridine (BrdU), inhibits differentiation in a number of systems. This agent blocks the synthesis of cell specific products without significantly affecting growth (1,5,11,31,51,54,55,58,59,60,62).In our previous studies on the development of the embryonic pancreas in vitro, we have shown that BrdU selectively inhibits the synthesis of the exocrine proteins at concentrations that have little if any effect on general protein, RNA or DNA synthesis or on the principal metabolic pathways (55). We also observed that these BrdU-treated pancreases develop large fluid-filled vacuoles linked by cells which appear similar to duct cells (55). We have further tested the possibility that these cells are in fact duct cells, by measuring the levels of alkaline phosphatase and carbonic anhydrase, enzymes which are characteristic for these cells: both of these enzymes are associated with tissues active in fluid transport (23,35); and in the pancreas they are localized primarily in the duct cells (10,21,36,56). The activities of these enzymes have been determined by conventional enzymatic methods, and their cellular location has been visualized by specific histochemical procedures. We have found that BrdU induces both alkaline phosphatase and carbonic anhydrase coincident with the formation of vacuoles. Both of the induced enzymes are localized preferentially in the epithelial cells lining the vacuoles. Thus in the presence of BrdU, cultured embryonic pancreases contain many cells that by ultrastructural, biochemical, and functional criteria are identical to normal duct cells. BrdU therefore appears to enhance dramatically the proportion of duct cells in the rudiment. This result is consistent with the existence of a pluripotent cell that is a precursor of the acinar cells, and may be equivalent to, or

Pathogenesis of bromodeoxyuridine‐induced cleft palate in hamster

“…How the transcription process manifests itself at the cellular level following BrdU exposure is, however, unclear. Various possibilities are outlined in the literature and may be arranged into three categories: 1) alteration in the cell cycle, which, in turn, would affect the growth and differentiation of the tissues (Bannigan and Langman, 1979;Bannigan, 1985Bannigan, , 1987; 2) chromosomal breakage (Kaback et al, 1964;Sutherland et al, 1985;Ackland et al, 1988); and 3) alteration in cytodifferentiation either directly or indirectly by affecting the cell membrane (Levis et al, 1971;Tsuboi and Baserga, 1973;Garcia et al, 1979;Maylie-Pfenninger and Jamieson, 19811, or the synthesis of extracellular matrix (Bischoff and Holtzer, 1970;Daniel, 1976;Ho et al, 1977;Giotta et al, 19801, or enzyme activity (Meuth and Green, 1974;Koyoma and Ono, 1971;Githens et al, 1977;Moscona and Moscona, 1979;Biggers et al, 1987). Bannigan and Langman (1979) and Bannigan (1985Bannigan ( , 1987 indicated that BrdU incorporation into DNA of the embryonic neuroepithelial cells resulted in the prolongation of the S-phase of the cell cycle, thus slowing the generation time and reducing the cell numbers, and eventually causing cell death.…”

Characterization of Endocrine Progenitor Cells and Critical Factors for Their Differentiation in Human Adult Pancreatic Cell Culture

“…Dilution of the incorporated BrdU as a result of further division of the labeled cells during subsequent culture may also decrease the number of BrdUpositive cells in CHIBs, particularly after early-phase labeling. Moreover, BrdU may have a negative effect on pancreatic cell differentiation (35). Thus, the numbers of BrdU-labeled endocrine cells may underestimate the differentiation of initially proliferating ductal cells.…”

5-Bromo-2-deoxyuridine activates DNA damage signalling responses and induces a senescence-like phenotype in p16-null lung cancer cells

“…Subsequently, BrdU became known as a differentiating agent owing to its effects on the morphology and phenotype of a wide range of cell types in vitro and in vivo, including normal chondrocytes, muscle, molar, brain, pancreatic and blood cells [15][16][17][18][19][20], and leukaemic and lung cancer cells [21][22][23][24]. More recently, the Ayusawa group [25,26] has reported that BrdU induces a senescent-like phenotype in both normal and transformed cells.…”