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ToxSci Advance Access published online on February 18, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg009
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received September 3, 2002; accepted December 6, 2002
© 2003 Society of Toxicology

Biotransformation and Toxicokinetics

Cadmium Uptake Kinetics in Rat Hepatocytes: Correction for Albumin Binding

Nicholas J. DelRaso 1*, B. D. Foy 2, J. M. Gearhart 3, J. M. Frazier 1

1 Operational Toxicology Branch, Human Effectiveness Directorate, Air Force Research Laboratory, Wright-Patterson AFB, OH 45433-7400
2 Department of Physics, Wright State University, Dayton, OH 45435
3 ManTech Environmental Technology, Inc., Dayton, OH 45433

* To whom correspondence should be addressed. E-mail: nicholas.delraso{at}he.wpafb.af.mil.


  Abstract

The relationship between cytotoxicity and kinetics of cadmium uptake was investigated in primary rat hepatocyte cultures. Primary rat hepatocytes were exposed to cadmium concentrations ranging from 1.0 to 80µM in albumin-free buffer or 32 to 8000µM in buffer containing physiological concentrations of bovine serum albumin (600µM) for 1 h and cellular toxicity was observed at 23 h post-exposure. Hepatocytes exposed to cadmium in the presence of albumin appeared less sensitive to cadmium toxicity when compared to cells exposed in the absence of albumin. The experimentally derived 23 h post-exposure EC50s for hepatocytes exposed to cadmium in the presence and absence of albumin was 65.5 ± 2.4µM and 14.3 ± 3.9µM, respectively. A Scatchard plot of cadmium binding to albumin suggested two high-affinity binding sites. The observed uptake of cadmium by hepatocytes in the absence and presence of albumin consisted of a composite fast uptake rate and cell membrane association (Component I), and a slow sustained uptake rate (Component II). Cadmium uptake rates in hepatocytes, based on total medium cadmium concentrations, indicated that Component II uptake rates were 4-times faster under albumin-free exposure conditions. However, when uptake rates were evaluated based on the calculated equilibrium free-cadmium concentration in the exposure buffer, uptake rates in hepatocytes exposed in the presence of albumin were 2-times faster. This faster cadmium uptake in the presence of albumin may result from diffusion limited non-equilibrium conditions occurring at the cell surface.

Cadmium, Hepatocytes, In Vitro, Albumin, Kinetics .


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