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The Role of ABCG2 in Mouse Embryonic Stem Cell Development
Citation:
Hoopes, M., S. Charla, H. Nichols, Mitch Rosen, S. Hunter, AND K. Chandler. The Role of ABCG2 in Mouse Embryonic Stem Cell Development. 10th World Congress Alternatives and Animal Use in the Life Sciences, Seattle, Washington, August 20 - 24, 2017.
Impact/Purpose:
As a xenobiotic transporter, modulation of ABCG2 is an important marker in high throughput assays. Data from our group also suggests regulation of ABCG2 might be a critical molecular initiating event associated with adverse development. Hence, consideration of ABCG2 function could be a consideration when creating adverse outcome pathways linked to developmental phenotype.
Description:
ABCG2 is a commonly studied efflux transporter. The role of ABCG2 during early development, however, is not clear. Previous studies suggested that regulation of ABCG2 could be associated altered differentiation in mouse embryonic stem cells (mESC) via altered redox status. ABCG2 activity was found to expand during early mESC differentiation. Pharmacological inhibition of ABCG2 was used, with and without xenobiotic exposure, to evaluate differentiation. Inhibition of ABCG2 in combination with chemicals predicted by ToxCast to regulate ABCG2 did not modify toxicity. Moreover, while inhibition of ABCG2 increased the toxicity of certain chemotherapeutics, it did not shift the toxicity of oxidative stressors. Hence, ABCG2 serves a protective role during development, although it’s role in regulating redox status is unclear. The hypothesis that regulation of ABCG2 by xenobiotics may be associated with altered differentiation could not be supported. (This abstract does not reflect EPA policy.)