| First Author | Elbling L | Year | 1993 |
| Journal | FASEB J | Volume | 7 |
| Issue | 15 | Pages | 1499-506 |
| PubMed ID | 7903262 | Mgi Jnum | J:16043 |
| Mgi Id | MGI:64138 | Doi | 10.1096/fasebj.7.15.7903262 |
| Citation | Elbling L, et al. (1993) P-glycoprotein regulates chemosensitivity in early developmental stages of the mouse. FASEB J 7(15):1499-506 |
| abstractText | 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. |
