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Title:Selenium: An Inhibitor of Tumor Growth in Vitro and in Vivo
Author(s):Poirier, Kenneth Allen
Department / Program:Food Science
Discipline:Food Science
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Health Sciences, Nutrition
Abstract:Tumor growth in Swiss ICR mice inoculated with 5 x 10('5) Ehrlich ascites tumor (EAT) cells was completely inhibited by intraperitoneal administration of 20 (mu)g selenium as Na(,2)SeO(,3) given 8 times over an 18 day period. This regimen did not affect growth in non-tumor-bearing mice. Sodium selenite was the most effective modulator of EAT cell growth in vivo (Na(,2)SeO(,3) >> Na(,2)Se, (Ch(,3))(,2)Se, Se-cystine) and of EAT cell viability in vitro (Na(,2)SeO(,3), SeO(,2) > Se-methionine, Se-cystine > Na(,2)SeO(,4)). Initiation of multiple selenium treatment had to be undertaken no later than 3 days following tumor cell inoculation. Single treatments of selenium were only moderately effective in inhibiting EAT growth when administered immediately following tumor cell inoculation.
Dietary selenium had a variable response on tumor incidence and survival time in EAT-bearing mice. Selenium had no effect on EAT incidence in mice fed purified L-amino acid diets supplemented with up to 5.0 ppm selenium as selenite. However, survival time was significantly increased in EAT-bearing mice fed a torula yeast diet supplemented with 2.5 or 5.0 ppm selenium as selenite. Gastric gavage of Na(,2)SeO(,3) similarly prolonged survival time in mice. However, intraperitoneal administration of Na(,2)SeO(,3) was three to four times more effective in prolonging survival time than either dietary or gavage administration.
Glutathione perioxidase activity was increased in both liver and EAT cells of mice fed selenium supplemented diets. However, this increased activity did not account for the observed inhibitory effect of selenium on EAT cell growth. Glutathione, reduced and oxidized, was not altered by selenium supplementation in vivo or in vitro. RNA, DNA, protein, and lipid levels in EAT cells were not altered by selenium treatment. However, RNA biosynthesis was decreased in both EAT and canine mammary tumors in vitro by Na(,2)SeO(,3). Selenodiglutathione (GSSeSG), a metabolite of selenium reduction, also significantly decreased RNA biosynthesis in EAT. GSSeSG was more effective than Na(,2)SeO(,3) in increasing the survival time of EAT-bearing mice and decreasing proliferation of SV 40 3T3 cells in vitro. This effect was not observed by other selenium, sulfur, or thiol containing compounds. It was concluded that the action of selenium on tumor cell propagation in vivo and in vitro was modulated at least in part through its reductive metabolite, selenodiglutathione.
Issue Date:1984
Description:153 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1984.
Other Identifier(s):(UMI)AAI8409825
Date Available in IDEALS:2015-05-13
Date Deposited:1984

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