ToxSci Advance Access originally published online on July 13, 2009
Toxicological Sciences 2009 111(2):247-253; doi:10.1093/toxsci/kfp151
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Effect of Dietary Selenium and Cigarette Smoke on Pulmonary Cell Proliferation in Mice
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* Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506
Health Supervision Institute of Chongqing Municipal Health Bureau, Chongqing, China
Graduate Center for Toxicology
Department of Animal and Food Sciences
¶ Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky 40506
1 To whom correspondence should be addressed at Graduate Center for Nutritional Sciences, 222 Funkhouser Building, University of Kentucky, Lexington, KY 40506-0054. Fax: (859) 323-0061. E-mail: hglauert{at}uky.edu.
Received May 8, 2009; accepted July 8, 2009
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Abstract |
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The objective of this study was to determine if dietary selenium could inhibit pulmonary cell proliferation in control and cigarette smoke-exposed female A/J mice. Selenium in the form of sodium selenite was supplemented to purified diets similar to the AIN-93M diet to yield 0.15, 0.5, or 2.0 mg selenium/kg diet. After 3 weeks, mice in each dietary group were divided into two subgroups; one used as control, whereas the other was exposed to cigarette smoke for five consecutive days. Mice from both groups were euthanized 3 days later. Mice were administered bromodeoxyuridine in the drinking water starting 5 days before the initiation of the smoke exposure and continuing until they were euthanized. After euthanasia, the left lung lobe was processed for histology and cell proliferation analysis. Cigarette smoke increased cell proliferation in the terminal bronchioles and large airways, but not in alveoli. High-selenium diets inhibited cell proliferation in the alveoli, terminal bronchioles and large airways areas in both control and smoke-exposed mice. Increasing the dietary selenium level led to increased selenium levels in the blood and lung, and increased glutathione peroxidase (GPx) activity in the lung. Cytochrome P-450 1A1 protein levels in the lung were increased by cigarette smoke but were not affected by dietary selenium. It is concluded that dietary selenium inhibits pulmonary cell proliferation in both control and cigarette smoke-exposed mice, indicating that selenium is inhibiting cell proliferation independently of smoke exposure, and that this inhibition may be related to selenium concentration and GPx activity in the lung.
Key Words: selenium; cigarette; smoke; cell proliferation; lung.