Date of Award
Doctor of Philosophy
Toxicology; Cell Biology;
M. Duane Enger
The role of glutathione (GSH) in cadmium cytotoxic response was investigated in human lung carcinoma A549 cells with coordinately high GSH levels and cadmium resistance. Depletion of cellular GSH in A549-T27 sensitized the cells to cadmium, indicating that GSH is involved in the cadmium cytoprotective response. Temporal studies showed that GSH is importantly involved in the early phase of the cadmium cytotoxic response. A high correlation between cadmium cytotoxicity and GSH levels which change as a function of cell growth stages provided strong evidence to support the above conclusions. Further study revealed that there are differential effects of cellular GSH depletion by different mechanisms on cellular metallothionein (MT) accumulation. Depletion of cellular GSH to equivalent levels using different agents produced differential cadmium cytotoxic responses. This observation suggested that the intracellular cysteine pool may limit MT accumulation. The cadmium cytoprotective effect is thus not simply correlated to total cellular cysteine content, but rather is related to competition between GSH and MT synthesis for a limiting pool of cysteine;Comparison of the cadmium cytotoxic responses in T20, a relatively cadmium sensitive variant, and T27, a relatively cadmium resistant variant of the A549 cell line has shown that the difference in cadmium cytotoxicity between the two variants is not due to their overall rates of MT accumulation, nor to a difference in their rates of cadmium accumulation. However, a difference in GSH metabolism in response to cadmium is observed (even though there are comparable initial GSH levels in the two variants) and may be one of the factors affecting overall cadmium cytotoxicity.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Kang, Yu-Jian, "The role of glutathione in cadmium cytotoxic response in human lung carcinoma A549 cells " (1989). Retrospective Theses and Dissertations. 9206.