Abstract
The discovery that one drug transporter, P-glycoprotein, decreases intracellular concentrations of many anticancer drugs explains how drug resistance could simultaneously develop to structurally unrelated compounds (1). These discoveries have focused attention on the kinetics of drug distribution within cells. Flow cytometry can be easily adapted to collect kinetic data on fluorescent compounds by recording time as one parameter.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Gottesman, M. M. and Pastan, I. (1988) The multidrug transporter, a double-edged sword J of Biol Chem. 263, 12,163–12,166
Gibaldi, M. and Perreir, D (1982) Pharmacokinetics Marcel Dekker, New York.
Dordal, M. S, Ho, A C, Jackson-Stone, M., Fu, Y. F., Goolsby, C. L., and Winter, J N (1995) Flow cytometric assessment of the cellular pharmacokinetics of fluorescent drugs. Cytometry 20, 307–314.
Dalmark, M. and Storm, H. H (1981) A Fickian diffusion transport process with features of transport catalysis. Doxorubicin transport in human red blood cells. J. Gen Physiol 78, 349–364
Summerhayes, I C, Lampidis, T. J., Bernal, S D, Nadakavukaren, J H., Nadakavukaren, K. K, Shepherd, E. L, and Chen, L B. (1982) Unusual retention of rhodamine 123 by mitochondria in muscle and carcinoma cells Proc Natl AcadSci USA 79, 5292–5296
Dessypris, E. N., Brenner, D E, Baer, M. R., and Hande, K R. (1988) Uptake and intracellular distribution of doxorubicin metabolites in B-lymphocytes of chronic lymphocytic leukemia Cancer Res 48, 503–506
Dordal, M. S., Jackson-Stone, M., Ho, A C, Winter, J. N., and Atkinson, A. J. J. (1994) Decreased intracellular compartmentahzation of doxorubicin in cell lines expressing P-glycoprotein J Pharmacol Exp Ther 271, 1286–1290.
Jackson-Stone, M, Fu, Y. F, Ho, A C, Winter, J N., and Dordal, M. S. (1994) Flow cytometric measurement of altered intracellular drug distribution in multidrug resistant cells. Clin Res. 42, 393A.
Dordal, M. S., Fu, Y. F., and Ho, A. C. (1996) P-glycoprotein decreases mitochondrial sequestration of rhodamine as well as increasing efflux. Proc Am. Assoc Cancer Res 37, 312.
Dordal, M S and Fu, Y. F. (1996) Cellular pharmacokinetics of innotecan in drug-sensitive and multidrug resistant cell lines. Proc Am Assoc. Cancer Res. 37, 429.
Roy, D, Munshi, C. B., Mi, Z., and Burke, T. G. (1995) Alteration of uptake and cytotoxicity of camptothecin drugs in MCF-7 breast cancer cells by human serum albumin. Proc. Am Assoc Cancer Res. 36, 444.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Dordal, M.S. (1998). Flow Cytometric Monitoring of Cellular Pharmacokinetics. In: Jaroszeski, M.J., Heller, R. (eds) Flow Cytometry Protocols. Methods in Molecular Biology™, vol 91. Humana Press, Totowa, NJ. https://doi.org/10.1385/0-89603-354-6:123
Download citation
DOI: https://doi.org/10.1385/0-89603-354-6:123
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-0-89603-354-2
Online ISBN: 978-1-59259-214-2
eBook Packages: Springer Protocols