Journal article
Effect of Dietary Selenium on the Promotion of Hepatocarcinogenesis by 3,3′, 4,4′-Tetrachlorobiphenyl and 2,2′, 4,4′, 5,5′-Hexachlorobiphenyl
Experimental biology and medicine (Maywood, N.J.), Vol.233(3), pp.366-376
03/2008
DOI: 10.3181/0708-RM-211
PMID: 18296742
Abstract
Polychlorinated biphenyls (PCBs) are persistent organic pollutants that have promoting activity in the liver. PCBs induce oxidative stress, which may influence carcinogenesis. Epidemiological studies strongly suggest an inverse relationship between dietary selenium (Se) and cancer. Despite evidence linking Se deficiency to hepatocellular carcinoma and liver necrosis, the underlying mechanisms for Se cancer protection in the liver remain to be determined. We examined the effect of dietary Se on the tumor promoting activities of two PCBs congeners, 3,3′, 4,4′-tetrachlorobiphenyl (PCB-77) and 2,2′, 4,4′, 5,5′-hexachlorobiphenyl (PCB-153) using a 2-stage carcinogenesis model. An AIN-93 torula yeast-based purified diet containing 0.02 (deficient), 0.2 (adequate), or 2.0 mg (supplemental) selenium/kg diet was fed to Sprague-Dawley female rats starting ten days after administering a single dose of diethylnitrosamine (150 mg/kg). After being fed the selenium diets for 3 weeks, rats received four i.p. injections of either PCB-77 or PCB-153 (150 μ mol/kg) administered every 14 days. The number of placental glutathione S-transferase (PGST)-positive foci per cm3 and per liver among the PCB-77–treated rats was increased as the Se dietary level increased. Unlike PCB-77, rats receiving PCB-153 did not show the same Se dose-response effect; nevertheless, Se supplementation did not confer protection against foci development. However, the 2.0 ppm Se diet reduced the mean focal volume, indicating a possible protective effect by inhibiting progression of preneoplastic lesions into larger foci. Cell proliferation was not inhibited by Se in the liver of the PCB-treated groups. Se did not prevent the PCB-77–induced decrease of hepatic Se and associated reduction in glutathione peroxidase (GPx) activity. In contrast, thioredoxin reductase (TrxR) activity was not affected by the PCBs treatment or by Se supplementation. These findings indicate that Se does not inhibit the number of PGST-positive foci induced during promotion by PCBs, but that the size of the lesions may be inhibited. The effects of Se on altered hepatic foci do not correlate with its effects on GPx and TrxR.
Details
- Title: Subtitle
- Effect of Dietary Selenium on the Promotion of Hepatocarcinogenesis by 3,3′, 4,4′-Tetrachlorobiphenyl and 2,2′, 4,4′, 5,5′-Hexachlorobiphenyl
- Creators
- Divinia N Stemm - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506;Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506;Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242;Department of Statistics, University of Kentucky, Lexington, Kentucky 40506;Research Reactor Center, University of Missouri, Columbia, Missouri 65201; andDepartment of Microbiology, Immunology, and Molecular Genetics, University of KentuckyJob C Tharappel - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506;Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506;Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242;Department of Statistics, University of Kentucky, Lexington, Kentucky 40506;Research Reactor Center, University of Missouri, Columbia, Missouri 65201; andDepartment of Microbiology, Immunology, and Molecular Genetics, University of KentuckyHans-Joachim Lehmler - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506;Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506;Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242;Department of Statistics, University of Kentucky, Lexington, Kentucky 40506;Research Reactor Center, University of Missouri, Columbia, Missouri 65201; andDepartment of Microbiology, Immunology, and Molecular Genetics, University of KentuckyCidambi Srinivasan - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506;Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506;Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242;Department of Statistics, University of Kentucky, Lexington, Kentucky 40506;Research Reactor Center, University of Missouri, Columbia, Missouri 65201; andDepartment of Microbiology, Immunology, and Molecular Genetics, University of KentuckyJ. Steven Morris - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506;Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506;Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242;Department of Statistics, University of Kentucky, Lexington, Kentucky 40506;Research Reactor Center, University of Missouri, Columbia, Missouri 65201; andDepartment of Microbiology, Immunology, and Molecular Genetics, University of KentuckyVickie L Spate - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506;Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506;Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242;Department of Statistics, University of Kentucky, Lexington, Kentucky 40506;Research Reactor Center, University of Missouri, Columbia, Missouri 65201; andDepartment of Microbiology, Immunology, and Molecular Genetics, University of KentuckyLarry W Robertson - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506;Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506;Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242;Department of Statistics, University of Kentucky, Lexington, Kentucky 40506;Research Reactor Center, University of Missouri, Columbia, Missouri 65201; andDepartment of Microbiology, Immunology, and Molecular Genetics, University of KentuckyBrett T Spear - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506;Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506;Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242;Department of Statistics, University of Kentucky, Lexington, Kentucky 40506;Research Reactor Center, University of Missouri, Columbia, Missouri 65201; andDepartment of Microbiology, Immunology, and Molecular Genetics, University of KentuckyHoward P Glauert - Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506;Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506;Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242;Department of Statistics, University of Kentucky, Lexington, Kentucky 40506;Research Reactor Center, University of Missouri, Columbia, Missouri 65201; andDepartment of Microbiology, Immunology, and Molecular Genetics, University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Experimental biology and medicine (Maywood, N.J.), Vol.233(3), pp.366-376
- DOI
- 10.3181/0708-RM-211
- PMID
- 18296742
- NLM abbreviation
- Exp Biol Med (Maywood)
- ISSN
- 1535-3702
- eISSN
- 1535-3699
- Language
- English
- Date published
- 03/2008
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
- Record Identifier
- 9984000933102771
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