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At least 757 records · Page 42Linked to original sources
PubMed1998

17 beta-Oestradiol and 1 alpha,25-dihydroxycholecalciferol modulate constitutive and bone matrix-induced interleukin-1 beta (IL-1 beta) production by peripheral blood mononuclear cells isolated from postmenopausal women.

Local production and release of interleukin-1 (IL-1) may be of importance for bone remodeling, since this cytokine is known to stimulate bone resorption. We have studied the effect of bone matrix constituents on IL-1 beta production by peripheral blood mononuclear cells (PBMCs) isolated from 20 postmenopausal non-osteoporotic women. Hydroxyapatite (0.5 mg/ml) and heat-denaturated collagen (25 micrograms/ml) stimulated IL-1 beta production 5-fold and 520-fold, respectively, compared to control (p < 0.01). In contrast, transforming growth factor-beta (TGF-beta, 10 ng/ml), a cytokine which is abundant in bone matrix, suppressed median IL-1 beta release to 13% of control value (p < 0.01). The bone matrix-induced changes in IL-1 beta production were modulated by 10 nmol/1 17 beta-oestradiol and 10 nmol/1 1 alpha,25-dihydroxy-cholecalciferol (1,25(OH)2D3). Specifically, 17 beta oestradiol stimulated constitutive IL-1 beta release with 89% (p < 0.01) and nullified the suppressive effect of TGF-beta. Moreover, 1,25(OH)2D3 had a synergistically stimulatory effect with both hydroxyapatite and collagen, although there was no effect of this hormone when added alone. The adherent cells were slightly more elongated after treatment with 1,25(OH)2D3 and collagen, while TGF-beta and 17 beta-oestradiol had no effect on cellular morphology. Addition of hydroxyapatite resulted in long and spindle-shaped cells, and phagocytosis of the particles occurred. The modulatory effects of oestrogen and vitamin D on constitutive and bone-matrix induced IL-1 beta production by PBMCs may be of importance for bone remodelling during postmenopausal bone loss and at a site of fracture.

Bone Matrix↗
PubMed1998

Beneficial effect of bisphosphonate during five years of treatment of severe osteogenesis imperfecta.

We report results of 2-5 y treatment with intravenous disodium pamidronate (APD) in three girls with severe osteogenesis imperfecta (OI). Treatment was given as monthly infusions. Additional oral 1,25-dihydroxy-cholecalciferol was given to compensate for a transient decrease in serum calcium levels. During treatment, DEXA measurements showed a gradual increase in bone density in all patients. All parameters analysed in serum (ALP, osteocalcin, PICP, ICTP) and in urine (deoxypyridinoline and pyridinoline) showed a decreased bone turnover. The two younger patients reported a major improvement in well-being, pain and activities of daily life. The effect on the older patient was less pronounced. No negative side effects in clinical or laboratory variables were observed. This study indicates that APD is of value in the symptomatic treatment of children with severe OI.

Absorptiometry, Photon↗
PubMed2005

Osteoprotegerin and bone mineral density in hemodiafiltration patients.

A newly identified cytokine, osteoprotegerin (OPG) appears to be involved in the regulation of bone remodeling. In vitro studies suggest that OPG, a soluble member of the TNF receptor family of proteins, inhibits osteoclastogenesis by interrupting the intercellular signaling between osteoblastic stromal cells and osteoclast progenitors. As patients with chronic renal failure (CRF) often have renal osteodystrophy (ROD), we investigated the role of osteoprotegerin (OPG) in ROD, and investigated whether there was any relationship between serum OPG, intact parathyroid (PTH) (iPTH), vitamin D, and trabecular bone. Serum OPG combined with iPTH might be a useful tool in the noninvasive diagnosis of ROD, at least in cases in which the range of PTH values compromises reliable diagnosis. Thirty-six patients on maintenance hemodiafiltration (HDF) and a control group of 36 age and sex matched healthy subjects with no known metabolic bone disease were studied. The following assays were made on serum: iPTH, osteocalcin (BGP), bone alkaline phosphatase, 25(OH)-cholecalciferol, calcium, phosphate, OPG, IGF-1, estradiol, and free testosterone. Serum Ca++, P, B-ALP, BGP, IGF-1, iPTH, and OPG levels were significantly higher in HDF patients than in controls, while DXA measurements and quantitative ultrasound (QUS) parameters were significantly lower. On grouping patients according to their mean OPG levels, we observed significantly lower serum IGF-1, vitamin D3 concentrations, and lumbar spine and hip bone mineral density in the high OPG groups. No correlation was found between OPG and bone turnover markers, whereas a negative correlation was found between serum OPG and IGF-1 levels (r=-0.64, p=0.032). Serum iPTH concentrations were positively correlated with bone alkaline phosphatase (B-ALP) (r=0.69, p=0.038) and BGP (r=0.92, p<0.001). The findings made suggest that an increase in OPG levels may be a compensatory response to elevated bone loss. The low bone mineral density (BMD) levels found in the high OPG group might have been due to the significant decrease in serum IGF-1 and vitamin D3 observed. In conclusion, the findings made in the present study demonstrate that increased OPG in hemodiafiltration patients is only partly due to decreased renal clearance. As it may partly reflect a compensatory response to increased bone loss, this parameter might be helpful in the identification of patients with a marked reduction in trabecular BMD.

Absorptiometry, Photon↗
PubMed1980

Aminoaciduria in chronic renal failure--its relationship to vitamin D and parathyroid status.

Fractional clearances of amino acids in 24 patients with chronic renal failure indicate that aminoaciduria is common and often severe. Eleven studies have also been carried out in ten patients with stable renal failure before and during treatment with different metabolites of vitamin D. Sequential measurements of fractional clearance of amino acids, plasma 25-hydroxy-vitamin D (25-(OH)D) and serum parathyroid hormone were made. All patients initially had hyperaminoaciduria, secondary hyperparathyroidism and osteomalacia. Treatment with 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) or 1 alpha-hydroxycholecalciferol (1 alpha(OH)D3) significantly improved amino acid reabsorption irrespective of the initial degree of aminoaciduria. Cholecalciferol or 25-hydroxycholecalciferol(25(OH)D3) improved amino acid transport in patients with initially mild hyperaminoaciduria, but not in patients with severe hyperaminoaciduria. Reduction in aminoaciduria during treatment with 25(OH)D3 may have depended on a variable ability to synthesize 1,25(OH)2D3. Changes in amino acid transport did not correlate with changes in serum parathyroid hormone. It is suggested that defective amino acid reabsorption in patients with chronic renal failure is due at least in part to deficiency of 1,25(OH)2D3.

Amino Acids↗
PubMed1982

Serum vitamin level maintenance in cancer patients on total parenteral nutrition.

The quantity of water and fat soluble vitamins required to maintain serum levels in cancer patients on total parenteral nutrition (TPN) has yet to be determined. A prospective evaluation of our current intravenous vitamin regimen during TPN was performed in order to define these requirements. Seventy-five patients receiving 97 TPN courses for seven to 60 days were studied. Serum levels of vitamins A (74 courses), B12 (85), folate (62), C (97), and 25-OH-cholecalciferol (25-OH-D) (9) were available for analysis. Daily vitamin intakes were recorded and serum levels were determined weekly. Restoration and maintenance of normal mean serum vitamin levels were achieved for all but 25-OH-D. However, analysis of individual courses in previously depleted patients revealed that serum levels were not restored in three patients (4%) for vitamin A and six patients (66%) for 25-OH-D. A TPN regimen designed to provide the following weekly vitamin quantities: A: 21,000 IU, D: 2100 IU, C: 3500 mg, B12: 126 micrograms, and folate: 7 mg will maintain mean serum vitamin levels for all but 25-OH-D. This regimen has the ability to uniformly restore and maintain vitamins B12, C, and folate in all patients but not in those patients previously deficient in vitamins A and D.

Adult↗
PubMed1989

Ovariectomy, dietary zinc, and bone metabolism in retired breeder rats.

Bone mineral turnover was studied in sham and ovariectomized (ovax) retired breeder rats after 16 wk of dietary treatment. Rats were fed either a commercial rat diet (CRD) containing high calcium and cholecalciferol or egg-white diets (EWD) containing 2 g Ca/kg, 1,25-(OH)2cholecalciferol (5 micrograms/kg), and either 10 or 200 mg zinc/kg. In rats fed EWD, high Zn enhanced femoral Zn deposition and concentration but did not affect serum Ca levels, bone mineral content (BMC), or turnover. Serum Ca levels and BMC were greater in sham rats and there was a gain in femoral Ca and phosphorus compared with the loss of these minerals in ovax rats. In CRD-fed ovax rats, values for these variables were similar to those of CRD-fed shams and there was no bone mineral loss. These data suggest that ovarian function may be a prerequisite for the beneficial effects of diets containing 1,25-(OH)2cholecalciferol and low Ca on bone metabolism.

Animals↗
PubMed2006

Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes.

Recent evidence suggests that vitamin D intakes above current recommendations may be associated with better health outcomes. However, optimal serum concentrations of 25-hydroxyvitamin D [25(OH)D] have not been defined. This review summarizes evidence from studies that evaluated thresholds for serum 25(OH)D concentrations in relation to bone mineral density (BMD), lower-extremity function, dental health, and risk of falls, fractures, and colorectal cancer. For all endpoints, the most advantageous serum concentrations of 25(OH)D begin at 75 nmol/L (30 ng/mL), and the best are between 90 and 100 nmol/L (36-40 ng/mL). In most persons, these concentrations could not be reached with the currently recommended intakes of 200 and 600 IU vitamin D/d for younger and older adults, respectively. A comparison of vitamin D intakes with achieved serum concentrations of 25(OH)D for the purpose of estimating optimal intakes led us to suggest that, for bone health in younger adults and all studied outcomes in older adults, an increase in the currently recommended intake of vitamin D is warranted. An intake for all adults of > or =1000 IU (25 microg) [DOSAGE ERROR CORRECTED] vitamin D (cholecalciferol)/d is needed to bring vitamin D concentrations in no less than 50% of the population up to 75 nmol/L. The implications of higher doses for the entire adult population should be addressed in future studies.

Age Factors↗
PubMed2005

Growth inhibition of carcinogen-transformed MCF-12F breast epithelial cells and hormone-sensitive BT-474 breast cancer cells by 1alpha-hydroxyvitamin D5.

Several studies have established the active form of vitamin D(3) as an effective tumor-suppressing agent; however, its antitumor activity is achieved at doses that are hypercalcemic in vivo. Therefore, less calcemic vitamin D(3) analog, 1alpha-hydroxy-24-ethyl-cholecalciferol (1alpha[OH]D5), was evaluated for its potential use in breast cancer chemoprevention. Previously, 1alpha(OH)D5 showed anticarcinogenic activity in several in vivo and in vitro models. However, its effects on growth of normal tissue were not known. The present study was conducted to determine the effects of 1alpha(OH)D5 on the growth of normal mouse mammary gland and normal-like human breast epithelial MCF-12F cells and to compare these effects with carcinogen-transformed MCF-12F and breast cancer cells. No significant difference was observed in the growth or morphology of cultured mouse mammary gland and MCF-12F cells in the presence of 1alpha(OH)D5. However, the transformed MCF-12F cells underwent growth inhibition (40-60%, P < 0.05) upon 1alpha(OH)D5 treatment as determined by cell viability assays. Cell cycle analysis showed marked increase (50%) in G-1 phase for cells treated with 1alpha(OH)D5 compared with the controls. Moreover, the percentage of cells in the synthesis (S) phase of cell cycle was decreased by 70% in transformed MCF-12F, BT-474 and MCF-7 cells. The growth arrest was preceded by an increase in expression of cell cycle regulatory proteins p21(Waf-1) and p27(Kip-1). In addition, differential expression studies of parent and transformed MCF-12F cell lines using microarrays showed that prohibitin mRNA was increased 4-fold in the transformed cells. These results indicate that the growth inhibitory effect of 1alpha(OH)D5 was achieved in both carcinogen-transformed MCF-12F and breast cancer cells at a dose that was non-inhibitory in normal-like breast epithelial cells.

Animals↗
PubMed1980

Do sunlight and vitamin D reduce the likelihood of colon cancer?

It is proposed that vitamin D is a protective factor against colon cancer. This hypothesis arose from inspection of the geographic distribution of colon cancer deaths in the U.S., which revealed that colon cancer mortality rates were highest in places where populations were exposed to the least amounts of natural light--major cities, and rural areas in high latitudes. The hypothesis is supported by a comparison of colon cancer mortality rates in areas that vary in mean daily solar radiation penetrating the atmosphere. A mechanism involving cholecalciferol (vitamin D3) is suggested. The possibility that an ecological fallacy or other indirect association explains the findings is explored.

Calcium↗
PubMed1978

Stimulatory effect of 1,25-dihydroxycholecalciferol-like substances from Solanum malacoxylon and Cestrum diurnum on phosphate transport in chick jejunum.

Extracts of the calcinogenic plants Solanum malocoxylon and Cestrum diurnum stimulate phosphate absorption by the jejunum of vitamin D-deficient chicks, as determined by everted gut sac technique. Their action on cellular pathways of transepithelial phosphate transport is indistinguishable thereby from that of cholecalciferol. Increased net absorption from the lumen was due to enhanced uptake of phosphate from the luminal side, while leakage of tissue phosphate in the opposite direction was apparently unaffected. Steep serosa/mucosa concentration gradients were observed as consequence of enhanced levels of transepithelial phosphate flux in the mucosa-to-serosa direction. With respect to their stimulatory action on phosphate absorption, the calcinogenic plant factors retained their biological activity when phosphate transport was depressed by a high strontium diet. Their action in overcoming the strontium inhibition of phosphate absorption, calcium-binding protein synthesis, and alkaline phosphatase activity, was comparable to the effect of 1,25-dihydroxycholecalciferol. On the basis of these biological responses, the action of the plant factors from Solanum malacoxylon and Cestrum diurnum provides further evidence for their close resemblance to the hormonally active sterol.

Animals↗
PubMed1978

Evidence for the promotion of bone mineralization by 1alpha,25-dihydroxycholecalciferol in the rat unrelated to the correction of deficiencies in serum calcium and phosphorus.

Concurrent administration of 1alpha,25-dihydroxycholecalciferol [1alpha,25-(OH)2-CC] to intact and thyroparathyroidectomized rats treated with ethane-1-hydroxy-1,1-diphosphonate (EHDP) prevented or reversed the EHDP-induced inhibition of bone mineralization as measured by changes in epiphyseal plate width and ash content of bone. An analog, 1alpha-droxycholecalciferol, was also effective. Recovery of bone after EHDP treatment was also significantly improved by administration of 1alpha,25-(OH)2-CC as evidenced by enhanced uptake of 45Ca by epiphyseal plates and decreased plate widths. Cholecalciferol (CC), ergocalciferol, dihydrotachysterol2, 5,6-trans-CC, 25-OH-CC, 5,6-Trans-25-OH-CC, and 1alpha24R,25-(OH)3-CC also blocked EHDP-induced epiphyseal plate widening, but required high, pharmacological dose levels. 24R,25- (OH)2-CC was inactive at doses up to 10 microgram/day. Since EHDP-treated rats are not deficient in calcium or phosphate, these data suggest that 1alpha,25-dihydroxycholecalciferol promoted bone mineralization independently of effects upon the intestinal absorption of calcium and phosphate.

Animals↗
PubMed1983

Normal egg hatchability requires the simultaneous administration to the hen of 1 alpha,25-dihydroxycholecalciferol and 24R,25-dihydroxycholecalciferol.

A previous report [Science 201, 835-837 (1978)] presented evidence that the combined and simultaneous administration of the cholecalciferol (D3) metabolites 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] and 24R,25-dihydroxycholecalciferol [24R,25(OH)2D3] to White Leghorn hens was necessary for embryo development and normal egg hatchability; in the absence of 24R,25(OH)2D3 none of the fertile eggs hatched. The present study extends this fundamental observation to a second species, the Japanese quail, Coturnix coturnix japonica and compares the biological actions of the two stereoisomers of the 24,25(OH)2 metabolite, namely the naturally occurring 24R,25(OH)2D3 and its unnatural epimer 24S,25(OH)2D3. Groups of 12-14 vitamin D-depleted adult female Japanese quail were mated with normal male quail and eight consecutive batches of eggs (25-41 eggs from each group) were placed in an egg incubator, and egg hatchability for the fertile eggs monitored on days 21 and 22. The egg hatchability (in percent +/- SD) for each group was: D3 (56.5% +/- 12.8); 1 alpha,25(OH)2D3 (1.3% +/- 2.5); 24R,25(OH)2D3 (29.6% +/- 3.1); 24R25(OH)2D3 + 1 alpha,25-(OH)2D3 (32.8%); and 24S,25(OH)2D3 + 1 alpha,25(OH)2D3 (7.2%). Also for all treatment groups the blood level of the expected vitamin D metabolites were in the normal range, and there were no significant differences in the embryo weights and eggshell thickness (of both hatched and unhatched eggs). These results indicate that the Japanese quail have the inherent capability to discriminate between the stereoisomers of 24,25(OH)2D3 and therefore strongly support the concept that only the naturally occurring 24R,25(OH)2D3 has an identifiable, unique biological role which is different from that of 1 alpha,25(OH)2D3.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Biological activity of 24,24-difluoro-25-hydroxycholecalciferol in chicks.

The biological activity of subcutaneously injected 24,24-difluoro-25-hydroxycholecalciferol was compared with that of 25-hydroxycholecalciferol in the vitamin D-deficient growing chick. 24,24-Difluoro-25-hydroxycholecalciferol is equal to 25-hydroxycholecalciferol in the stimulation of: 1) growth, 2) intestinal calcium absorption, 3) elevation of serum calcium and serum phosphorus, 4) healing of rachitic cartilage (radiography), and 5) mineralization of rachitic bone (bone ash). The response appears to be linear in the range of 13.0 to 325 pmol daily. Since 24,24-difluorocholecaliferol cannot be 24-hydroxylated to produce either 24,25-dihydroxycholecalciferol or 1,24,25-trihydroxycholecalciferol, while it can be 1 alpha-hydroxylated to produce 24,24-difluoro-1,25-dihydroxycholecalciferol, these results demonstrate that 24-hydroxylation is not required for the known functions of cholecalciferol in the chick.

Animals↗
PubMed1984

Effect of phosphate on the intestinal absorption of lead (203Pb) in chicks.

The effect of phosphate on the intestinal absorption of lead (203Pb2+) was examined in chicks. Absorption was determined by the in situ ligated duodenal loop technique. In one approach, diets differing in phosphate content were fed to 2-week-old chicks for a period of 7 days. With respect to the control group (1.06% P), a severe phosphate deficiency (0.16% P) decreased growth, CaBP synthesis and 203Pb absorption; a moderate phosphate deficiency (0.33% P) resulted in an increase in CaBP production and 203Pb absorption; and the high phosphate diet (2.12%) gave mean values for CaBP synthesis and 203Pb absorption intermediate between those from the chicks fed the 0.33 and 1.06% diets. 203Pb absorption was highly correlated with CaBP concentrations. In another approach, phosphate in varying concentrations was added directly to the dosing solution. In one study, phosphate addition (0.1 mM) depressed 203Pb absorption in rachitic and cholecalciferol-treated chicks. When the data were expressed in terms of absorption of the soluble 203Pb present in the intestinal lumen at the end of the absorption period, an effect of phosphate in addition to the precipitation of the insoluble lead salt was uncovered. In an experiment with normal chicks, it was observed that phosphate in the dosing solution at concentrations of 1 and 2 mM partially and significantly reversed the inhibitory effect of lower concentrations of phosphate (0.01 mM and 0.1 mM). These data demonstrate the complexity of the phosphate-lead interaction, in addition to directly showing an effect of dietary phosphate on intestinal lead absorption.

Animals↗
PubMed1985

Effects of different soybean meals on the incidence of tibial dyschondroplasia in the chicken.

Interexperimental variation in the incidence of tibial dyschondroplasia of chickens that occurred in studies on the effect of dietary calcium, phosphorus and cholecalciferol metabolites was apparent from previous reports from this laboratory. Since the source of commercial soybean meal used in the diets was known to change, studies were conducted to evaluate different sources of soybean meal on the incidence of tibial dyschondroplasia. A series of experiments demonstrated that the soybean meals from one source consistently produced a high incidence of tibial dyschondroplasia (34-69%); whereas soybean meals from a different source consistently produced low incidences (14-28%). This same relationship was found with soybean meals from these two plants produced a year apart. When the levels of two soybean meals that produced a high incidence of tibial dyschondroplasia were reduced in the diet from 35 to 24 12% the incidence of tibial dyschondroplasia was reduced from 60 and 69% to 25 and 20% to 15 and 10%, respectively. The most striking difference between the meals observed by chemical analysis was in the high antitrypsin and urease values of the meals that induced tibial dyschondroplasia. Chickens fed the soybean meal that reduced tibial dyschondroplasia also had reduced pancreas size in one experiment but not another. The soybean meals that induced tibial dyschondroplasia caused an increase in testes size but had no effect on liver, adrenal and thyroid size or plasma levels of calcium, phosphorus and triiodothyronine (T3). No difference in the utilization of the diets as measured by metabolizable energy values and lipid calcium, phosphorus or phytin phosphorus retention was found between the soybean meals that induced high or low incidence of tibial dyschondroplasia with chickens at 19-21 d of age.

Animal Feed↗
PubMed1988

Calcium and vitamin D in bone metabolism: analyses of their effects with a short-term in vivo bone model in rats.

A short-term in vivo system was developed to examine simultaneously bone formation and resorption, and the effects of dietary calcium and vitamin D on these processes. In experiment 1, 25 male Long-Evans rats were each implanted with two gelatin capsules containing mineralized bone (MB) powder subcutaneously in the thorax region. At 4, 6, 8, 10 and 12 d after implantation the acid phosphatase activity (resorption) increased significantly (P less than 0.01), whereas alkaline phosphatase activity (formation) did not change. In experiment 2, both MB and demineralized bone (DB) powder were implanted on contralateral dorsal sites of the thorax in 40 male Long-Evans rats and harvested after 7, 9, 11 and 13 d. Enzyme, mineral and histological assessment indicated bone formation in DB implants with bone resorption in MB implants. In experiment 3, the effects of dietary calcium (0.2 or 1.0%) and vitamin D (cholecalciferol at 300 ng/d or 1,25-dihydroxycholecalciferol [1,25(OH)2D3] at 75 ng/d) were examined using 40 male Long-Evans rats. These rats were implanted with both DB and MB powders and the implants were harvested on d 12. Both low (0.2%) dietary calcium and 1,25(OH)2D3 stimulated resorption of MB implants. Therefore, the physiological processes of bone formation and resorption were mimicked in this system of bone powder implants. Further, dietary calcium and 1,25(OH)2D3 were shown to modulate these processes.

Acid Phosphatase↗
PubMed1990

Ascorbic acid effects on vitamin D hormone metabolism and binding in guinea pigs.

Ascorbic acid deficiency in guinea pigs fed a vitamin D-replete diet caused a moderate reduction of Ca level in serum and bone; 25-hydroxy-cholecalciferol or 25-hydroxyergocalciferol (25-OHD) serum concentration tended to decline; renal 25-hydroxycholecalciferol-1-hydroxylase (1-OHase) activity decreased 50%; and 25-hydroxycholecalciferol-24-hydroxylase activity increased 1.6-fold. Chromatin 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] receptor concentration in the intestinal mucosa decreased 20-30%, and the percentage of occupied receptors decreased from 12-15% to 6-8%. Receptor affinity for 1,25-(OH)2D3 did not change (Kd = 0.24-0.26 nmol/L, Kd2 = 0.06-0.10 nmol/L), but the cooperativity coefficient decreased from 1.7 to 1.4. Vitamin C deficiency potentiated effects of vitamin D deprivation and impaired a restorative action of vitamin D. It was accompanied by a marked delay in the elevation of 25-OHD concentration in serum as well as decreased 1-OHase activity in kidneys and a lower concentration of occupied 1,25-(OH)2D3 receptors in the intestinal mucosa. The data demonstrate a critical role for ascorbic acid in vitamin D metabolism and binding.

25-Hydroxyvitamin D 2↗
PubMed1993

Influence of dietary calcium and vitamin D on colon epithelial cell proliferation and 1,2-dimethylhydrazine-induced colon carcinogenesis in rats fed high fat diets.

We investigated whether increased levels of dietary calcium and vitamin D could inhibit colon carcinogenesis in rats injected with a single dose of 1,2-dimethylhydrazine. Rats were given a single subcutaneous injection (200 mg/kg body wt) 2 wk before they were fed purified diets containing 20% fat for 32 wk. Diets contained one of three levels of calcium (5, 10 or 15 g/kg diet) as calcium gluconate and one of three levels of vitamin D (0.025, 0.05 or 0.1 mg/kg diet) as cholecalciferol in a 3 x 3 factorial design. Rats receiving the highest level of vitamin D had greater plasma concentrations of 25-hydroxy-vitamin D. Autoradiographic examination of [3H]thymidine-treated rats demonstrated that a higher dietary level of calcium as well as higher levels of vitamin D significantly affected cellular kinetic indices. The total tumor incidence and tumor incidence in the distal colon was 45% lower in rats fed the highest level of both calcium and vitamin D compared with the other eight groups, although this decrease was not statistically significant (P = 0.12). The possible importance of these observations is discussed.

1,2-Dimethylhydrazine↗