Abstract

The synthetic halogenated pyrimidine analog, 5-bromo-2′-deoxyuridine (BrdU), is a marker of DNA synthesis. This exogenous nucleoside has generated important insights into the cellular mechanisms of the central nervous system development in a variety of animals including insects, birds, and mammals. Despite this, the detrimental effects of the incorporation of BrdU into DNA on proliferation and viability of different types of cells has been frequently neglected. This review will summarize and present the effects of a pulse of BrdU, at doses ranging from 25 to 300 µg/g, or repeated injections. The latter, following the method of the progressively delayed labeling comprehensive procedure. The prenatal and perinatal development of the cerebellum are studied. These current data have implications for the interpretation of the results obtained by this marker as an index of the generation, migration, and settled pattern of neurons in the developing central nervous system. Caution should be exercised when interpreting the results obtained using BrdU. This is particularly important when high or repeated doses of this agent are injected. I hope that this review sheds light on the effects of this toxic maker. It may be used as a reference for toxicologists and neurobiologists given the broad use of 5-bromo-2′-deoxyuridine to label dividing cells.

Highlights

  • The thymidine analogue 5-bromo-2 -deoxyuridine (BrdU) is a pyrimidine 2 -deoxyribonucleoside compound having 5-bromouracil as the nucleobase

  • The dose of 300 μg/g of BrdU produced the most detrimental effects (Figure 1). These results have indicated that a single low dose of BrdU (25 to 75 μg/g) does not alter the proliferative behavior of the neuroepitelial neuroblasts

  • The synthetic halogenated pyrimidine analogue BrdU is a marker of DNA synthesis

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Summary

Introduction

The thymidine analogue 5-bromo-2 -deoxyuridine (BrdU) is a pyrimidine 2 -deoxyribonucleoside compound having 5-bromouracil as the nucleobase. The controversy is generated when BrdU-immunoreactive cells can be explained by processes not associated with cell division (DNA repair or apoptotic events) and doublecortin-stained cells do not present substantial proliferative activity. These results can be interpreted as the existence of young neurons, which maturation, in the human brain, might take years. A slow and delayed development of young neurons may replace neurogenetic processes in the adulthood [11,12] Despite these data, BrdU has been considered that it is relatively benign and the consequences on the progression of the cell-cycle, migration, and fate are usually negligible or understated. To know whether there are any differences between BrdU or tritiated thymidine ([3H]TdR) labeling, it was determined whether the administration of several doses of both markers, by a progressively delayed cumulative labeling method in utero, modify the developmental timetables and neurogenetic gradients of PCs and DCN neurons

The Thymidine Analogue 5-Bromo-2 -Deoxyuridine
Effect of Bromodeoxyuridine Exposure on the Cerebellar Neuroepithelium
Conclusions

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