The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 1983-1984

Hepatotoxicity: An In Vitro Approach to the Study of Toxicity and Membrane Interactions of Cadmium Using Cultured Rat Hepatocytes

Daniel Acosta Jr., PhD, and M.B. Sorensen, PhD
University of Texas, Austin, Texas

Problem

The presence of calcium in the incubation medium of cultured rat hepatocytes may reduce cell toxicity induced by reactions with cadmium. This study would focus on interactions of these two chemicals at the cell membrane, and may lead to a better understanding of cadmium-induced toxicity.

Effects on three types of membranes -- in situ plasma membranes, isolated plasma membranes and artificial membranes -- will be evaluated in the following basis:

Morphology: Changes in the internal and external plasma membranes of cultured cells will be examined following exposure to calcium with and without calcium. Scanning electron microscopy and whole cell examination will be used to quantify the severity of damage, and to determine the effect of calcium in altering the damage.

Plasma Membrane Perturbations: Fluorescence techniques will be used to determine whether calcium exerts a stabilizing effect on plasma membranes exposed to cadmium.

Biochemistry: The ability of calcium to alter cadmium-induced effects will be examined in studies of enzymes and ion leakage from cells and changes in the flow of calcium and cadmium through cells.

Impact of the Research

Effects of cadmium and calcium interactions at the level of the cell membrane may lead to a better understanding of cellular toxicity and membrane function.