Involvement of cellular sulfhydryls in the selenite-mediated growth inhibition of canine mammary tumor cells in culture
Kuchan, Matthew John
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https://hdl.handle.net/2142/21493
Description
Title
Involvement of cellular sulfhydryls in the selenite-mediated growth inhibition of canine mammary tumor cells in culture
Author(s)
Kuchan, Matthew John
Issue Date
1991
Doctoral Committee Chair(s)
Layman, Donald K.
Department of Study
Food Science and Human Nutrition
Discipline
Food Science and Human Nutrition
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Cell
Biology, Animal Physiology
Agriculture, Animal Culture and Nutrition
Language
eng
Abstract
A selenium responsive canine mammary tumor cell line (CMT-13) was utilized to examine the mechanism by which selenium as selenite inhibits the growth of some tumor cells. The ability of supplemental selenite to inhibit the in vitro growth of CMT-13 cells increased with culture density, concentration of selenite and length of exposure to selenite.
Cellular retention of selenium was not a prerequisite for growth inhibition. Reduced glutathione (GSH), required for the detoxification of excess selenite, was considered to be of potential importance. The intracellular molar ratio of GSH to selenium was shown to be a sensitive determinant of the severity of growth inhibition. These data suggested a limited ability to detoxify excess selenium in cells with a low GSH/Se.
To test this conclusion, CMT-13 cells with differing ratios of GSH to Se were generated. Cellular concentrations of the end product of selenium detoxification, dimethyl selenide (DMS), were higher in cells with a depressed ratio of GSH to Se. Pulse/chase experiments revealed a greater rate of removal of selenium from CMT-13 cells with a lower ratio of GSH to Se. Thus, a decreased rate of metabolism was not associated with a depressed ratio of GSH to Se.
Cellular concentrations of glutathione selenopersulfide (GSSeH) were increased in cells with depressed ratios of GSH to Se. The accumulation of this seleno-compound implies that CMT-13 cells have a limited ability to increase selenium detoxification relative to the rate of selenium uptake.
Supplemental GSH was found to markedly alter the growth response of CMT-13 cells to supplemental selenite (12.6 $\mu$M). GSH (100 $\mu$M) protected cells from the growth inhibition normally caused by selenite. Cellular retention of selenium was depressed by GSH preincubation. In contrast, retention was dramatically increased by the simultaneous addition of selenite and GSH.
Finally, the incubation of CMT-13 cells with thiol blockers impermeable to biomembranes decreased cellular retention of selenium. These data suggest that cell membrane thiols are necessary for selenium uptake. Treatment of CMT-13 cells resulted in specific alterations in the peptide thiol pattern. (Abstract shortened with permission of author.)
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