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Title:Metabolic Factors Affecting the Ability of Selenium to Inhibit the Growth of Canine Mammary Tumor Cells
Author(s):Santoro, Maxine Fico
Department / Program:Food Science
Discipline:Food Science
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Health Sciences, Nutrition
Abstract:Two neoplastic (CMT-13 and CMT-11) and a non-neoplastic primary culture (NCM) of canine mammary cells were used to assess the mechanism by which selenium inhibits cellular growth. The order of sensitivity to supplemental selenium was CMT-13 $>>$ CMT-11 $>>$ NCM cells. The ability of selenium to inhibit growth was also dependent upon plating density, length of incubation, and form of selenium, with selenodiglutathione (SDG) $>>$ selenite $>$ selenomethionine.
NCM and CMT-11 cells incubated with selenite (12.8 uM) were able to reduce selenium to a nontoxic form after 24 hours of incubation as indicated by lack of depression in growth, increased ability to form dimethyl selenide, and induction of enzymes which reduce selenium and maintain glutathione status. In contrast, selenium sensitive CMT-13 cells incubated for 24 hours with identical concentrations of selenite had a depression of growth, decreased ability to form dimethyl selenide, a dramatic depression in glutathione reductase (GRED) activity and decreased ability to induce glutathione. Incubation of CMT-13 cells with SDG (3.2 uM) resulted in a more dramatic reduction in both GRED and glutathione than occurred with selenite. These results can not be explained by complete inhibition of protein biosynthesis because glutathione peroxidase (GPX) activity was increased in all cell lines incubated with selenite or SDG (3.2 uM).
Supplementing CMT-13 cells with GSH (100 uM) for 48 hours prior to treatment reversed the growth inhibition induced by selenite (6.4 uM) or SDG (6.4 uM). Thus, the ability of cells to maintain adequate glutathione status partially determines a cells' susceptibility to selenium. Retention studies demonstrate that the intracellular form of selenium and movement to the nucleus is an important factor in susceptibility to selenium because although NCM cells retain more selenium, they are least sensitive to this trace element.
Finally, incubation of CMT-13 cells with selenite (12.8 uM) and SDG (6.4 uM) resulted in loss of peptides suggesting that the inhibitory action of selenium on tumor cell growth in vitro was modulated by SDG possibly via a depression in selected proteins. Autoradiographic analysis of peptides of cells incubated with $\sp{75}$Se-selenomethionine suggest that the decreased cytotoxicity of this seleno-compound may be due to random incorporation into protein thereby reducing the necessity for reductive detoxification. (Abstract shortened with permission of author.)
Issue Date:1987
Type:Text
Language:English
Description:184 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1987.
URI:http://hdl.handle.net/2142/77459
Other Identifier(s):(UMI)AAI8721751
Date Available in IDEALS:2015-05-13
Date Deposited:1987


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