Interindividual variation in the metabolism of arsenic in cultured primary human hepatocytes
Section snippets
Primary cultures of human hepatocytes
Hepatocytes were isolated as previously described Hamilton et al., 2001, LeCluyse et al., 2000 from normal hepatic tissue obtained from the Tissue Procurement and Analysis Core Facility at the University of North Carolina at Chapel Hill. Samples of normal liver were collected with patient consent during resections performed at North Carolina Memorial Hospital of the University of North Carolina at Chapel Hill or were obtained from non-transplantable donor livers. Study protocols for tissue
Functional characterization of cultured primary human hepatocytes
In preliminary studies, we examined the metabolic integrity and redox status of freshly isolated cells suspended in supplemented Williams' medium E (7.5 × 105 viable cells per ml) and of adherent cells cultured for up to 5 days in the same medium (7.5 × 105 viable cells per well in 1 ml medium). The effect of time in culture on the capacity of cells to metabolize iAs was also examined. Freshly plated monolayers contained a relatively large number of condensed apoptotic cells. These cells
Discussion
The work reported here examines qualitative and quantitative aspects of the variation of iAs metabolism in human liver using cultured primary hepatocytes from eight donors. Primary cultures of human hepatocytes have been widely used to study xenobiotic metabolism in vitro LeCluyse, 2001, Meunier et al., 2000. Under optimized culture conditions, primary hepatocytes retain differentiated structure and exhibit metabolic properties of normal liver. For example, in cultured primary human
Acknowledgements
S.B.W. is a postdoctoral fellow in the Curriculum in Toxicology, University of North Carolina at Chapel Hill and is supported by Training Grant T901915 of the U.S. Environmental Protection Agency-University of North Carolina Toxicology Research Program. M.S. is supported by NIH grant ES09941, US EPA Cooperative Agreement CR829522, and a Clinical Nutrition Research Center Grant DK 56350. This manuscript has been reviewed in accordance with the policy of the National Health and Environmental
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These authors contributed equally to the research described in this paper.