FASEB J. Pierce now sold as Thermo Scientific
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Elbling, L.
Right arrow Articles by Micksche, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Elbling, L.
Right arrow Articles by Micksche, M.

The FASEB Journal, Vol 7, 1499-1506, Copyright © 1993 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

P-glycoprotein regulates chemosensitivity in early developmental stages of the mouse

L Elbling, W Berger, A Rehberger, T Waldhor and M Micksche
Institute for Tumor Biology-Cancer Research, University of Vienna, Austria.

The multidrug resistance (MDR) P-glycoprotein (P-gp) is an active transporter associated with chemoresistance of tumor cells. A fundamental aspect not yet entirely clarified is the physiological role of MDR-P-gp in normal mammalian tissues. In this paper we report that multidrug (chemo)resistance is already present in mouse oocytes and early cleavage embryos. Expression of MDR-specific P-gp is detectable by antibody (C219) staining from the primary oocyte onward to the eight- cell embryo. MDR-mRNA is demonstrated in mature oocytes using an Mdr1- specific cDNA probe. Functional activity of P-gp is shown by the efficacy of MDR reversers (verapamil or quinidine) in enhancement of: 1) drug accumulation (daunomycin) in all stages investigated, 2) drug cytotoxicity (daunomycin or mitomycin c-induced developmental impairment) in two-cell embryos cultured for 24 h, and 3) drug cytokinesis-blocking activity (cytochalasin D; our recent findings demonstrate cytochalasins to be substrates for P-gp and to indicate the presence of MDR by their microfilament-disrupting action on cycling cells) in four- and eight-cell embryos cultured for 24 h. Furthermore, functional involvement of P-gp in vivo is demonstrated. Concurrent administration of verapamil increases doxorubicin-induced developmental impairment in the zygote stage during the first cleavage cycle in pregnant females. Results provide evidence that MDR-P-gp has an efficient protective function in early reproduction.


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Hamdoun and D. Epel
Embryo stability and vulnerability in an always changing world
PNAS, February 6, 2007; 104(6): 1745 - 1750.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1993 by The Federation of American Societies for Experimental Biology.