Long-term study of ovine pulmonary adenocarcinogenesis in sheep with marginal vs. sufficient nutritional selenium supply: Results from computed tomography, pathology, immunohistochemistry, JSRV-PCR and lung biochemistry

The impact of selenium (Se) in carcinogenesis is still debatable due to inconsistent results of observational studies, recent suspicion of diabetic side effects and e.g. dual roles of glutathione peroxidases (GPx). Previously, our group introduced long-term studies on lung carcinogenesis using the j...

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Published in:	Journal of trace elements in medicine and biology Vol. 27; no. 4; pp. 391 - 399
Main Authors:	Humann-Ziehank, Esther, Renko, Kostja, Bruegmann, Michael L., Devi, Vemuri Rama, Hewicker-Trautwein, Marion, Andreae, Arnim, Ganter, Martin
Format:	Journal Article
Language:	English
Published:	Germany Elsevier GmbH 01-10-2013
Subjects:	Animals Carcinogenesis Cell Proliferation Dietary Supplements Disease Models, Animal Glutathione Peroxidase - genetics Glutathione Peroxidase - metabolism GPx Immunohistochemistry Lung Lung - enzymology Lung - metabolism Polymerase Chain Reaction Pulmonary Adenomatosis, Ovine - genetics Pulmonary Adenomatosis, Ovine - metabolism Pulmonary Adenomatosis, Ovine - pathology Selenium Selenium - administration & dosage Selenium - deficiency Selenium - metabolism Sheep Sheep model Time Factors Tomography, X-Ray Computed Selenium Carcinogenesis Lung GPx Sheep model
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Summary:	The impact of selenium (Se) in carcinogenesis is still debatable due to inconsistent results of observational studies, recent suspicion of diabetic side effects and e.g. dual roles of glutathione peroxidases (GPx). Previously, our group introduced long-term studies on lung carcinogenesis using the jaagtsiekte sheep retrovirus (JSRV) induced ovine pulmonary adenocarcinoma (OPA) as an innovative animal model. The present report describes the results of sufficient (0.2mg Se/kg dry weight (dw)) vs. marginal (<0.05mg Se/kg dw) nutritional Se supply on cancer progression over a two-year period in 16 animals. Computed tomography (CT) evaluation of lung cancer progression, final pathological examination, evidence of pro-viral JSRV-DNA in lung, lymph nodes and broncho-alveolar lavage cells as well as biochemical analysis of Se, GPx1 and thioredoxin reductase (TrxR) activity in lung tissue were recorded. Additionally, immunohistochemical determination of GPx1 expression in unaffected and neoplastic lung cells was implemented. The feeding regime caused significant differences in Se concentration and GPx1 activity in lung tissue between groups, whereas TrxR activity remained unaffected. JSRV was evident in broncho-alveolar lavage cells, lung tissue and lung lymph nodes. Quarterly executed CT could not demonstrate differences in lung cancer proliferation intensity. Necropsy and histopathology substantiated CT findings. Immunohistochemical analysis of GPx1 in lung tissue suggested a coherency of GPx1 immunolabelling intensity in dependence of tumour size. It was concluded that the model proved to be suitable for long-term studies of lung cancer proliferation including the impact of modifiable nutritional factors. Proliferation of OPA was unaffected by marginal vs. sufficient nutritional Se supply.
ISSN:	0946-672X 1878-3252
DOI:	10.1016/j.jtemb.2013.03.002