Compound commonly used to detect proliferating cells
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Chemical compound
Bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU, BUdR, BrdUrd, broxuridine) is a synthetic nucleoside analogue with a chemical structure similar to thymidine. BrdU is commonly used to study cell proliferation in living tissues[1] and has been studied as a radiosensitizer[2] and diagnostic tool in people with cancer.[3]
During the S phase of the cell cycle (when DNA replication occurs), BrdU can be incorporated in place of thymidine in newly synthesized DNA molecules of dividing cells.[4] Cells that have recently performed DNA replication or DNA repair can be detected with antibodies specific for BrdU using techniques such as immunohistochemistry or immunofluorescence.[5] BrdU-labelled cells in humans can be detected up to two years after BrdU infusion.[6]
Because BrdU can replace thymidine during DNA replication, it can cause mutations, and its use is therefore potentially a health hazard.[citation needed] However, because it is neither radioactive nor myelotoxic at labeling concentrations, it is widely preferred for in vivo studies of cancer cell proliferation.[7][8] However, at radiosensitizing concentrations, BrdU becomes myelosuppressive, thus limiting its use for radiosensitizing.[2]
BrdU differs from thymidine in that BrdU substitutes a bromine atom for thymidine's CH3 group. The Br substitution can be used in X-ray diffraction experiments in crystals containing either DNA or RNA. The Br atom acts as an anomalous scatterer and its larger size will affect the crystal's X-ray diffraction enough to detect isomorphous differences as well.[9][10]
Bromodeoxyuridine releases gene silencing caused by DNA methylation.[11]
BrdU can also be used to identify microorganisms that respond to specific carbon substrates in aquatic[12] and soil[13] environments. A carbon substrate added to the incubations of environmental samples will cause the growth of microorganisms that can utilize that substrate. These microorganisms will then incorporate BrdU into their DNA as they grow. Community DNA can then be isolated and BrdU-labeled DNA purified using an immunocapture technique.[14] Subsequent sequencing of the labeled DNA can then be used to identify the microbial taxa that participated in the degradation of the added carbon source.
However, it is not certain whether all microbes present in an environmental sample can incorporate BrdU into their biomass during de novo DNA synthesis. Therefore, a group of microorganisms may respond to a carbon source but go undetected using this technique. Additionally, this technique is biased towards identifying microorganisms with A- and T-rich genomes.
DNA with BrdU transcribes as usual DNA, with guanine included in RNA as a complement to BrdU.[15]
^Lehner, Bernadette; Sandner, Beatrice; Marschallinger, Julia; Lehner, Christine; Furtner, Tanja; Couillard-Despres, Sebastien; Rivera, Francisco J.; Brockhoff, Gero; Bauer, Hans-Christian; Weidner, Norbert; Aigner, Ludwig (2011). "The dark side of BrdU in neural stem cell biology: Detrimental effects on cell cycle, differentiation and survival". Cell and Tissue Research. 345 (3): 313–28. doi:10.1007/s00441-011-1213-7. PMID 21837406. S2CID 756261.
^ abRusso A, Gianni L, Kinsella TJ, Klecker RW, Jenkins J, Rowland J, Glatstein E, Mitchell JB, Collins J, Myers C (1984). "Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors". Cancer Res. 44 (4): 1702–5. PMID 6704976.
^Dolbeare, F (May 1995). "Bromodeoxyuridine: a diagnostic tool in biology and medicine, Part I: Historical perspectives, histochemical methods and cell kinetics". The Histochemical Journal. 27 (5): 339–69. doi:10.1007/BF02389022. PMID 7657555. S2CID 21785471.
^Kee, N; S Sivalingam; R Boonstra; J.M Wojtowicz (March 2002). "The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis". Journal of Neuroscience Methods. 115 (1): 97–105. doi:10.1016/S0165-0270(02)00007-9. hdl:1807/357. PMID 11897369. S2CID 17572667.
^Konishi, Teruaki; Takeyasu, Akihiro; Natsume, Toshiyuki; Furusawa, Yoshiya; Hieda, Kotaro (2011). "Visualization of Heavy Ion Tracks by Labeling 3'-OH Termini of Induced DNA Strand Breaks". Journal of Radiation Research. 52 (4): 433–40. Bibcode:2011JRadR..52..433K. doi:10.1269/jrr.10097. PMID 21785232.
^Eriksson, Peter; Ekaterina Perfilieva; Thomas Björk-Eriksson; Ann-Marie Alborn; Claes Nordborg; Daniel A. Peterson; Fred H. Gage (1998). "Neurogenesis in the adult human hippocampus". Nature Medicine. 1313-1317. 4 (11): 1313–1317. doi:10.1038/3305. PMID 9809557.
^Fujimaki, Takamitsu; Masao Matsutani; Osamu Nakamura; Akio Asai; Nobuaki Funada; Morio Koike; Hiromu Segawa; Kouichi Aritake; Takanori Fukushima; Shuntaro Houjo; Akira Tamura; Keiji Sano (29 June 2006). "Correlation Between Bromodeoxyuridine- Labeling Indices and Patient Prognosis in Cerebral Astrocytic Tumors of Adults". Cancer. 67 (6): 1629–1634. doi:10.1002/1097-0142(19910315)67:6<1629::AID-CNCR2820670626>3.0.CO;2-E. PMID 2001552.
^Hoshino, Takao; Tadashi Nagashima; Judith Murovic; Ellen M. Levin; Victor A. Levin; Stephen M. Rupp (1985). "Cell Kinetic Studies of In Situ Human Brain Tumors With Bromodeoxyuridine". Cytometry. 6 (6): 627–632. doi:10.1002/cyto.990060619. PMID 2998714.
^Peterson, M. R.; Harrop, S. J.; McSweeney, S. M.; Leonard, G. A.; Thompson, A. W.; Hunter, W. N.; Helliwell, J. R. (1996). "MAD Phasing Strategies Explored with a Brominated Oligonucleotide Crystal at 1.65Å Resolution". Journal of Synchrotron Radiation. 3 (Pt 1): 24–34. doi:10.1107/S0909049595013288. PMID 16702655.
^Beck, Tobias; Gruene, Tim; Sheldrick, George M. (2010). "The magic triangle goes MAD: Experimental phasing with a bromine derivative". Acta Crystallographica Section D. 66 (4): 374–80. doi:10.1107/S0907444909051609. PMC 2852301. PMID 20382990.
^Weiss RA (2013). "On the concept and elucidation of endogenous retroviruses". Philos. Trans. R. Soc. Lond. B Biol. Sci. 368 (1626): 20120494. doi:10.1098/rstb.2012.0494. PMC 3758183. PMID 23938748.
^Tada, Yuya; Grossart, Hans-Peter (2013). "Community shifts of actively growing lake bacteria after N-acetyl-glucosamine addition: improving the BrdU-FACS method". The ISME Journal. 8 (2): 441–454. doi:10.1038/ismej.2013.148. ISSN 1751-7362. PMC 3906810. PMID 23985742.
^Borneman J (1999). "Culture-independent identification of microorganisms that respond to specified stimuli". Appl. Environ. Microbiol. 65 (8): 3398–400. Bibcode:1999ApEnM..65.3398B. doi:10.1128/AEM.65.8.3398-3400.1999. PMC 91510. PMID 10427025.
^Urbach, Ena; Kevin L. Vergin; Stephen J. Giovannoni (March 1999). "Immunochemical Detection and Isolation of DNA from Metabolically Active Bacteria". Applied and Environmental Microbiology. 65 (3): 1207–1213. Bibcode:1999ApEnM..65.1207U. doi:10.1128/AEM.65.3.1207-1213.1999. PMC 91166. PMID 10049885.
^Hill BT, Baserga R (1975). "Effect of 5-bromodeoxyuridine on the transcriptional properties of the genome in WI-38 human diploid fibroblasts". Chem. Biol. Interact. 10 (5): 363–375. doi:10.1016/0009-2797(75)90058-7. PMID 1095238.
Bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU, BUdR, BrdUrd, broxuridine) is a synthetic nucleoside analogue with a chemical structure similar to thymidine...
proliferative index include mitotic indexing, thymidine-labeling index, bromodeoxyuridine assay, the determination of fraction of cells in various phases of...
Kinase. "Induction of Endogenous Virus and of Thymidline Kinase by Bromodeoxyuridine in Cell Cultures Transformed by Friend Virus" (PDF). Archived (PDF)...
proliferation can be measured this way in lymphoproliferative disorders. Bromodeoxyuridine (BrdU) is another thymidine analog that is often used for the detection...
lack one of these genes. Thus, a cell lacking TK is resistant to bromodeoxyuridine (BrdU) and a cell lacking HGPRT is resistant to 6-thioguanine (6-TG)...
androgens and a lack of external male genitalia. Neural injections of Bromodeoxyuridine (BrdU) were applied to males of both groups to test for neurogenesis...
staining.[citation needed] Hoechst 33342 and 33258 are quenched by bromodeoxyuridine (BrdU), which is commonly used to detect dividing cells. Hoechst 33342...
drugs in animals. Examples of these studies include injection of bromodeoxyuridine for proliferation tracing, Apelin-13 for cerebral ischemia, and α-interferon...
dyed. The Giemsa staining was able to stain due to the presence of bromodeoxyuridine analogous base which was introduced to the desired chromatid. The...
doing an experiment in which the cells were treated in vivo with bromodeoxyuridine. In other experiments in mouse, it has been shown that the lifespan...
overcomes the limitations of traditional approaches (e.g. the classic Bromodeoxyuridine (BrdU) labeling technique has been used to identify slow-cycling cells...
1127. PMID 13860748. S2CID 1606140. Kuhn HG, Cooper-Kuhn CM (2007). "Bromodeoxyuridine and the detection of neurogenesis". Curr Pharmaceutical Biotechnol...
examples, see ), and nonfolate-sensitive groups, which are induced by bromodeoxyuridine (BrdU) or distamycin A, an antibiotic that preferentially binds to...
Claire; Jackie Hunter, A.; Thorndyke, Michael C. (1998). "Patterns of bromodeoxyuridine incorporation and neuropeptide immunoreactivity during arm regeneration...
parental DNA strands with a DNA label such as tritiated thymidine or bromodeoxyuridine (BrdU). These types of DNA labels will incorporate into the newly...
Merrick CJ (December 2015). "Transfection with thymidine kinase permits bromodeoxyuridine labelling of DNA replication in the human malaria parasite Plasmodium...
new method of non-radioactive labelling, based on incorporation of bromodeoxyuridine into single-stranded probes. The method was used to localise satellite...
typically involve incorporating modified nucleotides (such as BrdU, bromodeoxyuridine) into the nascent DNA, then fluorescently detecting it. As replication...