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a Henry Wellcome Laboratory for Biogerontology,
b Institute of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom;
c Department of Biological Sciences, University of Durham, Durham, United Kingdom
Key Words. Embryonic stem cells • Differentiation • Antioxidant defense • Peroxides DNA strand break • DNA repair • P-glycoprotein
Correspondence: Prof. Thomas von Zglinicki, Henry Wellcome Laboratory for Biogerontology, Newcastle General Hospital, University of Newcastle upon Tyne, Newcastle upon Tyne NE4 6BE, U.K. Telephone: 44-191-256-3310; Fax: 44-191-256-3445; e-mail: t.vonzglinicki{at}ncl.ac.uk
A very small number of embryonic stem (ES) cells gives rise to all tissues of the embryo proper. This means that ES cells should be equipped with highly efficient mechanisms to defend themselves against various stresses and to prevent or repair DNA damage. One of these mechanisms is a high activity of a verapamil-sensitive multidrug efflux pump. Because reactive oxygen species are a major source of DNA damage, we further tested the idea that murine ES cells might differ from their more differentiated counterparts by high levels of antioxidant defense and good DNA strand break repair capacity. This was confirmed by comparing cellular peroxide levels, total antioxidant capacity, and activity of radiation-induced strand break repair between murine ES cells and embryoid bodies or embryonic fibroblasts. Using microarrays and confirmation by reverse transcription–polymerase chain reaction, we identified several candidate antioxidant and stress-resistance genes that become downregulated during differentiation of ES cells into embryoid bodies.
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