Journal of Drug Metabolism & Toxicology
Open Access
ISSN: 2157-7609
+44-20-4587-4809
ISSN: 2157-7609
+44-20-4587-4809
Dan Rudin
Tanzania
Research Article
Gemcitabine Cytotoxicity: Interaction of Efflux and Deamination
Author(s): Dan Rudin, Liang Li, Nifang Niu, Krishna R. Kalari, Judith A. Gilbert, Matthew M. Ames and Liewei WangDan Rudin, Liang Li, Nifang Niu, Krishna R. Kalari, Judith A. Gilbert, Matthew M. Ames and Liewei Wang
Gemcitabine is a cytidine analogue used in the treatment of various solid tumors. Little is known about how gemcitabine and its metabolites are transported out of cells. We set out to study the efflux of gemcitabine and the possible consequences of that process in cancer cells. We observed the efflux of gemcitabine and its deaminated metabolite, 2',2'-difluorodeoxyuridine (dFdU) using high performance liquid chromatography and tandem mass spectrometry (LC-MS/MS) after gemcitabine treatment. Non-selective ABCCtransport inhibition with probenecid significantly increased intracellular dFdU concentrations, with a similar trend observed with verapamil, a non-selective ABCB1 and ABCG2 transport inhibitor. Neither probenecid nor verapamil altered intracellular gemcitabine levels after the inhibition of deamination with tetrahydrourudine, suggesting that efflux of dFdU, but not gemcitabine, was .. View More»
DOI:
10.4172/2157-7609.1000107