Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hummel, DM; Thiem, U; Höbaus, J; Mesteri, I; Gober, L; Stremnitzer, C; Graça, J; Obermayer-Pietsch, B; Kallay, E.
Prevention of preneoplastic lesions by dietary vitamin D in a mouse model of colorectal carcinogenesis.
J Steroid Biochem Mol Biol. 2013; 136(12):284-288
Doi: 10.1016/j.jsbmb.2012.09.003
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- Obermayer-Pietsch Barbara
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- Abstract:
- Colorectal cancer (CRC) is one of the leading causes of cancer morbidity and mortality in Western countries. One of the risk factors for colorectal tumorigenesis is vitamin D insufficiency. The aim of this study was to establish whether increasing dietary vitamin D intake can prevent or delay development of chemically induced preneoplastic lesions in the colon of mice. We fed six weeks old female C57BL/6J mice (n=28) with increasing vitamin D3 concentrations (100, 400, 1000, 2500, 5000IU/kg diet). To induce dysplasia, a preneoplastic lesion, we injected mice with the carcinogen azoxymethane (10mg/kg) intraperitoneally, followed by three cycles of 2% dextran sodium sulfate salt, a tumor promoter, in the drinking water. To test our hypothesis that high vitamin D intake prevents formation of preneoplastic lesions, we have investigated the effect of increasing dietary vitamin D on development of premalignant colorectal lesions, serum 25-hydroxyvitamin D3 (25-D3) levels, and expression of renal vitamin D system genes. Dietary vitamin D concentration correlated inversely with dysplasia score (Spearman's correlation coefficient, ρ: -0.579, p=0.002) and positively with serum 25-D3 levels (ρ: 0.752, p=0.001). Increasing dietary vitamin D concentration beyond 1000IU/kg led to no further increase in circulating 25-D3 levels, while the dysplasia score leveled out at ≥2500IU/kg vitamin D. High dietary vitamin D intake led to increased renal mRNA expression of the vitamin D catabolizing enzyme cyp24a1 (ρ: 0.518, p=0.005) and decreased expression of the vitamin D activating enzyme cyp27b1 (ρ: -0.452, p=0.016), protecting the body from toxic serum levels of the active vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25-D3). Our data showed that increasing dietary vitamin D intake is able to prevent chemically induced preneoplastic lesions. The maximum impact was achieved when the mice consumed more than 2500IU vitamin D/kg diet. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cholecalciferol - administration & dosage
- Colorectal Neoplasms - metabolism
- Dietary Supplements - adverse effects
- Female -
- Mice -
- Mice, Inbred C57BL -
- Precancerous Conditions - metabolism
- Find related publications in this database (Keywords)
- Vitamin D
- Colorectal cancer
- Dysplasia
- Chemoprevention
- cyp24a1
- cyp27b1