Effect of 5-(125)Iiodo-2'-deoxyuridine uptake on the proliferation and pluripotency of human embryonic stem cells.
Summary of "Effect of 5-(125)Iiodo-2'-deoxyuridine uptake on the proliferation and pluripotency of human embryonic stem cells."
Abstract Purpose: Human embryonic stem cells (hESC) hold a great potential for regenerative medicine because, in principle, they can differentiate into any cell type found in human body. In addition, studying the effect of ionizing radiation (IR) on hESC may provide valuable information about the response of human cells to IR exposure in their most naive state, as well as the consequences of IR exposure on the development of organisms. However the effect of IR, in particular radionuclide uptake, on the pluripotency, proliferation and survival of hESC has not been extensively studied. Methods: In this study we treated cultured hESC with 5-[(125)I]iodo-2'-deoxyuridine ((125)IdU), a precursor of DNA synthesis. Then we measured the expansion of colonies and expression of pluripotency markers in hESC. Results: We found that uptake of 125IdU was similar in both hESC and HT1080 human fibrosarcoma cells. However, treatment with 0.1 μCi/ml (125)IdU for 24 hours resulted in complete death of the hESC population; whereas HT1080 cancer cells continued to grow. Treatment with a tenfold lower dose (125)IdU (0.01 μCi/ml) resulted in colonies of hESC becoming less defined with numerous cells growing in monolayer outside of the colonies showing signs of differentiation. Then we analyzed the expression of pluripotency markers (octamer-binding transcription factor 4 (Oct-4) and stage-specific embryonic antigen-4 (SSEA4)) in the surviving hESC. We found that hESC in the surviving colonies expressed pluripotency markers at levels comparable with those in the non-treated controls. Conclusions: Our results provide important initial insights into the sensitivity of hESC to IR, and especially that produced by the decay of an internalized radionuclide.
Affiliation
Journal Details
This article was published in the following journal.
Name: International journal of radiation biology
ISSN: 1362-3095
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22676300
- DOI: http://dx.doi.org/10.3109/09553002.2012.700435
Medical and Biotech [MESH] Definitions
Deoxyuridine
2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies.
Neurotransmitter Uptake Inhibitors
Drugs that inhibit the transport of neurotransmitters into axon terminals or into storage vesicles within terminals. For many transmitters, uptake determines the time course of transmitter action so inhibiting uptake prolongs the activity of the transmitter. Blocking uptake may also deplete available transmitter stores. Many clinically important drugs are uptake inhibitors although the indirect reactions of the brain rather than the acute block of uptake itself is often responsible for the therapeutic effects.
Hemicholinium 3
A potent inhibitor of the high affinity uptake system for CHOLINE. It has less effect on the low affinity uptake system. Since choline is one of the components of ACETYLCHOLINE, treatment with hemicholinium can deplete acetylcholine from cholinergic terminals. Hemicholinium 3 is commonly used as a research tool in animal and in vitro experiments.
Desmoglein 2
A CALCIUM-dependent adhesion molecule of DESMOSOMES that also plays a role in embryonic STEM CELL proliferation.
Hek293 Cells
A cell line generated from human embryonic kidney cells that were tranformed with human adenovirus type 5.
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