Carcinogenesis Advance Access published online on July 17, 2007
Carcinogenesis, doi:10.1093/carcin/bgm165
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Published by Oxford University Press 2007.
Selenium status alters tumour differentiation but not incidence or latency of pancreatic adenocarcinomas in Ela-TGF-
p53+/– mice
1 Department of Comparative Medicine
2 Institute of Pathology
3 Institute of Ecological Chemistry, GSF Research Centre for Environment and Health, Neuherberg
4 II. Med. Klinik, Klinikum Rechts der Isar, Technical University, München
5 Hahn Meitner Institute, Dept. Molecular Trace Element Research in the Life Sciences, Berlin, Germany
* Corresponding Author: e-mail: brielmeier{at}gsf.de
Genetic predisposition and environmental factors act in concert in the pathogenesis of multi-factorial diseases. Selenoproteins represent fundamental anti-oxidative systems for the maintenance of cellular redox homeostasis, which is altered in various disease processes. Optimal function of selenoproteins requires availability of sufficient amounts of the essential trace element selenium, but in many countries the nutritive selenium supply is regarded insufficient. Supplemental selenium has been shown to have cancer-protective effects in a variety of experimental settings and clinical studies.
Pancreatic carcinoma has so far not been tested as an end point in such studies. We thus investigated the influence of supplemental nutritive selenium on pancreatic carcinogenesis in selenium deficient animals by use of a genetically defined disease model. Over a period of 800 days, all animals (n = 131) in the study developed tumours. Within this time, the mean total tumour latency was not influenced by the selenium status (471 vs 472 days). Also, the mean latency of pancreatic carcinomas (n = 83) was not influenced (464 vs 466 days). In contrast, the percentage of pancreatic tumors within all tumours was lower in the selenium-deficient group (55 vs 70%). A highly significant difference in the differentiation grade of the pancreatic tumours was evident between the two groups: selenium deficient mice (n = 33) developed predominantly undifferentiated anaplastic carcinomas (26 anaplastic vs 7 differentiated) whereas in the selenium-supplemented group (n = 50) mainly well-differentiated carcinomas were detected (20 anaplastic vs 30 differentiated). These data point at a new role of the trace element selenium in carcinogenesis.
Key Words: Selenium • pancreas • carcinoma • differentiation
Received March 16, 2007; revised July 9, 2007; accepted July 12, 2007.