Different effects of bromodeoxyuridine and [3H]thymidine incorporation into DNA on cell proliferation, position, and fate.
As markers of DNA synthesis, [(3)H]thymidine ([(3)H]dT) and the later developed analog bromodeoxyuridine (BrdU) have revolutionized our ability to identify dividing cells and follow their fate in various tissues, including the nervous system. However, the effect of the incorporation of these molecules into DNA on cell proliferation, migration, differentiation, and function is not fully understood. Here, we compare the number and distribution of labeled cells in the cerebral cortex of postnatal macaque monkeys exposed to either [(3)H]dT or BrdU as embryos. The large size and prolonged brain development in this species allows higher resolution of cellular events and more accurate discrimination between the two methods. Our analysis revealed substantial differences in the number and distribution of labeled cells. The data indicate that random incorporation of the thymidine analog BrdU into the genes of dividing cells makes the fate of postmitotic neurons more prone to unpredictable errors than the incorporation of the more natural DNA constituent nucleotide [(3)H]dT. These findings have implications for the interpretation of results obtained by BrdU as an index of the number of neurons produced, and their migration, placement, subsequent connectivity, function, and survival.
Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Alvaro
A
Duque
Pasko
P
Rakic
D000367:Age Factors; D000818:Animals; D001931:Brain Mapping; D001973:Bromodeoxyuridine / Q000378:metabolism*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects*; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000187:drug effects; D005260:Female; D008253:Macaca mulatta; D008297:Male; D018709:Statistics, Nonparametric; D013936:Thymidine / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000187:drug effects; D014316:Tritium / Q000493:pharmacokinetics*
D014316:Tritium; D004247:DNA; D001973:Bromodeoxyuridine; D013936:Thymidine