7%) and two in the 400 IU/kg group (33 4%) were vitamin D insuffi

7%) and two in the 400 IU/kg group (33.4%) were vitamin D insufficient. All the other animals could be considered to have adequate 25-D3 levels. Serum calcium concentrations remained relatively stable and did not correlate with serum selleck chem Crizotinib 25-D3 levels (data not shown). Systemic levels of the active 1,25-D3 are regulated by the kidneys; therefore, we measured gene expression of the vitamin D activating enzyme 25-hydroxyvitamin D3 1��-hydroxylase (cyp27b1), the vitamin D degrading enzyme 1,25-hydroxyvitamin D3 24-hydroxylase (cyp24a1), and the vitamin D receptor (vdr) by qRT-PCR. High dietary vitamin D intake increased cyp24a1 (��: 0.518, p = 0.005) and inhibited cyp27b1 (��: ?0.452, p = 0.016) gene expression. Furthermore, cyp27b1 expression correlated negatively with serum 25-D3 levels (��: ?0.

419, p = 0.026, Fig. 4, Table 2). The expression of vdr was not influenced either by diet or serum 25-D3 levels. Fig. 4 High dietary vitamin D increases cyp24a1, decreases cyp27b1 and does not affect vdr expression. Effect of increasing vitamin D concentration in the diet on renal cyp24a1 (A), cyp27b1 (B) and vdr (C) expression. Circles represent relative Discussion The aim of this study was to find the?expression of … 4. appropriate (lowest) dietary vitamin D level that would prevent formation of premalignant lesions in a mouse model of chemically induced colonic tumorigenesis. To our knowledge this is the first study investigating the effect of dose-dependency of vitamin D intake on preventing AOM/DSS-induced colonic tumorigenesis in mice.

We could show unequivocally that increasing vitamin D intake was able to delay formation of chemically induced low grade preneoplastic lesions and even prevent development of high grade dysplasia in the colon. We observed a very clear inverse correlation between dysplasia score and higher vitamin D intake as well as serum 25-D3 levels. Our data support the hypothesis that increasing vitamin D in the diet has chemopreventive effects on chemically induced precursors of colorectal tumors in mice. This effect seems to plateau at an intake of 2500 IU vitamin D/kg diet or higher. The effect of vitamin D, its metabolites and vitamin D analogues on colonic tumorigenesis in mice was investigated in several studies, however, the results are contradictory.

Majority of the studies that were not able to show any preventing or delaying effect of vitamin D and its analogues on colorectal tumorigenesis used vitamin D-sufficient control groups. In these studies, control diets contained 1000 IU/kg vitamin D [18,19], a level that is probably already chemopreventive. Our study, similar to the data presented by Fleet et al. [20], shows that Entinostat 1000 IU vitamin D/kg diet provides 25-D3 serum levels substantially higher than 30 ng/ml. Nevertheless there were reports for the effectiveness of vitamin D even compared with standard control diet, e.g. the study by Fichera et al.

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