Search

In addition to its recognized role in bone health, recent studies point to vitamin D functions in other tissues, including the pancreas. We tested the association between the vitamin D status and glucose and lipid homeostasis in a school-based, cross-sectional survey of a representative sample of youth. We measured fasting plasma insulin, glucose, total cholesterol (TC), triglycerides (TG), HDL cholesterol (HDL-C) apolipoproteins (apo) A1 and B, and 25-hydroxyvitamin D [25(OH)D] concentrations in 878 boys and 867girls. The 25(OH)D concentrations (mean [+ or -] SD) were 45.9 [+ or -] 12.2 nmol/L in boys and 45.9 [+ or -] 13.0 nmol/L in girls. More than 93% of youth had suboptimal ( doi: 10.3945/jn.109.112250.

The major circulating form of vitamin D is 25-hydroxycholecalciferol [25(OH)D3], which is delivered to target tissues in complex with the serum vitamin D binding protein (DBP). We recently observed that mammary cells can metabolize 25(OH)D3 to 1,25-dihydroxycholecalciferol [1,25[(OH).sub.2]D3], the vitamin D receptor (VDR) ligand, and the objective of our study was to elucidate the mechanisms by which the 25(OH)D3-DBP complex is internalized by mammary cells prior to metabolism. Using fluorescent microscopy and temperature-shift techniques, we found that T-47D breast cancer cells rapidly internalize DBP via endocytosis, which is blunted by receptor-associated protein, a specific inhibitor of megalinmediated endocytosis. Endocytosis of DBP was associated with activation of VDR by 25(OH)D3 but not 1,25[(OH).sub.2]D3 (as measured by induction of the VDR target gene, CYP24). We also found that megalin and its endocytic partner, cubilin, are coexpressed in normal murine mammary tissue, in nontransformed human mammary epithelial cell lines, and in some established human breast cancer cell lines. To our knowledge, our studies are the first to demonstrate that mammaryderived cells express megalin and cubilin, which contribute to the endocytic uptake of 25(OH)D3-DBP and activation of the VDR pathway.

Dihydroxycholecalciferol bound to its receptor functions as a potent antimitotic, prodifferentiating, proapoptotic hormone in different cell types and tissues. Epidemiological studies have linked low human serum concentrations of the vitamin D precursor hydroxycholecalciferol to colorectal cancer incidence. We have demonstrated in human colorectal tissue and cells the conversion of the precursor to dihydroxycholecalciferol, as well as the existence of the vitamin D catabolic pathway. These findings suggest a role for the colonic vitamin D system in tumor prevention. Low calcium intake has been found to be associated with human colorectal cancer incidence. In mice fed calcium equivalent to a low human intake, the degradative vitamin D pathway was increased, mainly in the ascending colon. Refeeding the mice high levels of vitamin D and calcium lowered tissue 25-hydroxycholecalciferol 24-hydroxylase activity, but only replenishment of folic acid normalized expression of the degradative pathway completely. Normalization occurred also when mice consuming low calcium diets were fed soy or the phytoestrogen genistein. These results indicate that colonic vitamin D synthesis is not only under stringent control of nutritional calcium, but also of folate, a methyl donor, which suggests epigenetic control of vitamin D hydroxylases. KEY WORDS: * colonic vitamin D hydroxylases * dietary calcium and folate * vitamin D degradation * phytoestrogens * epigenetic regulation

This article provides a review of the evidence identifying the factors related to vitamin D status in adolescents. The prevalence of vitamin D deficiency based on 25-hydroxyvitamin D [25(OH)D] of KEY WORDS: * vitamin D * adolescents * bone density * bone accrual * parathyroid hormone

The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber, high-fruit and vegetable, low-fat diet on the recurrence of adenomatous polyps in the large bowel. Detailed dietary intake and supplement use data were collected at baseline and at each of 4 annual study visits. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 y. Recurrence was found in 754 of the 1905 trial participants. We evaluated the association between calcium and vitamin D intake and adenomatous polyp recurrence after adjusting for intervention group, age, gender, nonsteroidal anti-inflammatory drug use, total energy intake, and the interaction of gender and intervention group. Vitamin D models were also adjusted for the location of the clinic site. Dietary variables were adjusted for total energy intake via the residual method. There were no overall significant associations between adenoma recurrence and dietary calcium intake [odds ratio (OR) for the 5th compared with the lowest quintile - 0.91 ; 95% CI = 0.67-1.23; P-trend = 0.68], total calcium intake (OR = 0.86; 95% CI = 0.62-1.18; P-trend = 0.20), or dietary vitamin D intake (OR = 0.93; 95% CI = 0.69-1.25; P-trend = 0.43) averaged over follow-up. Total vitamin D intake was weakly inversely associated with adenoma recurrence (OR = 0.84; 95% CI = 0.62-1.13; P-trend = 0.03). Supplemental calcium and vitamin D use during follow-up also were inversely associated with adenoma recurrence (OR for any compared with no use = 0.82; 95% CI = 0.68-0.99; and OR = 0.82; 95% CI - 0.68-0.99; for calcium and vitamin D, respectively). Slightly stronger associations were noted for the prevention of multiple recurrences. Our analyses did not suggest a significant effect modification between total calcium and total vitamin D intake (P = 0.14) on risk for adenoma recurrence. This trial cohort provides some evidence that calcium and vitamin D may be inversely associated with adenoma recurrence. KEY WORDS: * calcium * vitamin D * Polyp Prevention Trial * colorectal adenomas

It has been more than 3 decades since the first assay assessing circulating 25-hydroxyvitamin D [25(OH)D] in human subjects was performed and led to the definition of 'normal' nutritional vitamin D status, i.e., vitamin D sufficiency. Sampling human subjects, who appear to be free from disease, and assessing 'normal' circulating 25(OH)D levels based on a Gaussian distribution of these values is now considered to be a grossly inaccurate method of identifying the normal range. Several factors contribute to the inaccuracy of this approach, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary intake recommendations for vitamin D. The current adult recommendations for vitamin D, 200-600 IU/d, are very inadequate when one considers that a 10-15 min whole-body exposure to peak summer sun will generate and release up to 20,000 IU vitamin D-3 into the circulation. We are now able to better identify sufficient circulating 25(OH)D levels through the use of specific biomarkers that appropriately increase or decrease with changes in 25(OH)D levels; these include intact parathyroid hormone, calcium absorption, and bone mineral density. Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D [less than or equal to] 80 nmol or 32 [micro]g/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation. KEY WORDS: * vitamin D * 25-hydroxyvitamin D * parathyroid hormone * vitamin D requirement * bone mineral density * calcium absorption

Identification of the mechanisms involved in the pathology of nutrient deficiency provides an understanding of nutrient functions, their role in metabolism, and interactions between nutrients. However, evidence has emerged in recent years that low (suboptimal) intakes of micronutrients are associated with an elevated risk of chronic diseases. The description of micronutrient associations with chronic disease as a deficiency disease does not capture the complexity of these relations. It implies a significant oversimplification of this relation and detracts from the need for development of new approaches to this area of study. Epidemiologic study designs are essential for progress in understanding the micronutrient--chronic-disease relations, and these are described. Two areas wherein epidemiological tools could be incorporated into experimental designs have been vitamin D and prostate cancer, and vitamin D and colon cancer. In each case, biomarkers of exposure, intermediary markers, and mechanisms have been identified and could be implemented in new experimental designs. Measures of exposure would be improved by incorporation of measurements of vitamin D status such as serum 25-hydroxyvitamin D measurements. Several intermediary markers are discussed and may be useful in the characterization of responses. Such developments should aid in the interpretation of studies and identify vitamin D, as well as calcium intakes, that will aid in the prevention of prostate and colon cancer. KEY WORDS: * vitamin D * prostate cancer * colon cancer * biomarkers * epidemiology

Global high prevalence of vitamin D insufficiency and re-emergence of rickets and the growing scientific evidence linking low circulating 25-hydroxyvitmain D to increased risk of osteoporosis, diabetes, cancer, and autoimmune disorders have stimulated recommendations to increase sunlight (UVB) exposure as a source of vitamin D. However, concern over increased risk of melanoma with unprotected UVB exposure has led to the alternative recommendation that sufficient vitamin D should be supplied through dietary sources alone. Here, we examine the adequacy of vitamin D intake worldwide and evaluate the ability of current fortification policies and supplement use practices among various countries to meet this recommendation. It is evident from our review that vitamin D intake is often too low to sustain healthy circulating levels of 25-hydroxyvitmain D in countries without mandatory staple food fortification, such as with milk and margarine. Even in countries that do fortify, vitamin D intakes are low in some groups due to their unique dietary patterns, such as low milk consumption, vegetarian diet, limited use of dietary supplements, or loss of traditional high fish intakes. Our global review indicates that dietary supplement use may contribute 6-47% of the average vitamin D intake in some countries. Recent studies demonstrate safety and efficacy of community-based vitamin D supplementation trials and food staple fortification introduced in countries without fortification policies. Reliance on the world food supply as an alternative to UVB exposure will necessitate greater availability of fortified food staples, dietary supplement use, and/or change in dietary patterns to consume more fish. KEY WORDS: * vitamin D intake * 25-hydroxyvitamin D * food fortification * dietary supplements * vitamin D dietary requirements

From its inaugural value in 1941, the Recommended Dietary Allowance (RDA) for adults for vitamin D has remained close to 400 IU (10 [micro]g) level. This original recommended intake was based on the observation that the amount of vitamin D activity in a teaspoon of cod liver oil was sufficient to prevent rickets in infants. Since that time until 1997, determination of vitamin D requirements and status was more conjecture than science. In 1997, when the recommended intake level of vitamin D was set as an adequate intake value rather than an RDA, much has been learned about metabolism of vitamin D. The circulating metabolite 25-hydroxyvitamin D is the major static indicator of vitamin D status. Using its response to diet in the absence of sun exposure, a dose--response study suggests a mean requirement of at least 500 IU (12.5 [micro]g) from which an RDA could be set. Other factors may need adjustment, such as sun exposure and body fat. However, functional indicators of status are needed. The role of vitamin D in calcium metabolism (i.e., calciotropic functions) is better understood; bone turnover and parathyroid hormone are potential indicators. Vitamin D has noncalciotropic functions arising from extrarenal synthesis of the active metabolite 1,25 dihydroxyvitamin D involving cell proliferation and immunity, from which function indicators of status may be derived. Despite gaps in our knowledge, there are data from which new dietary reference intake values for vitamin D may be set. KEY WORDS: * vitamin D * requirement * dietary reference intakes * functional indicators * calciotropic * noncalciotropic

We analyzed the characteristics of young infants diagnosed with vitamin D deficiency in early infancy at 2 medical centers in Turkey. In this retrospective, cross-sectional study, the clinical, biochemical, and radiographic findings of infants who were diagnosed with vitamin D deficiency at KEY WORDS: * vitamin D deficiency * vitamin D * hypocalcemia

Vitamin D is a conditionally required nutrient traditionally thought to influence physiology as the metabolite 1,25-dihydroxyvitamin D [1,25[(OH).sub.2] D] by binding to the vitamin D receptor (VDR) and stimulating the transcription of genes through direct VDR-DNA interactions. However, over the past 15 y research has demonstrated that 1,25[(OH).sub.2] D, as well as other steroid hormones, can rapidly stimulate ion fluxes and activate protein kinases by transcription-independent mechanisms. This review summarizes recent research on the rapid actions of 1,25[(OH).sub.2] D and identifies questions that remain to be answered in this area. KEY WORDS: * kinase * ion flux * vitamin D

Epidemiologic studies suggest that nutritional phytoestrogens contained in soy are causally related to protection against hormone-dependent cancers. The incidence of colorectal cancer is at least 30% lower in women than in men in the United States. This suggests that estrogen and, conceivably, nutritional phytoestrogens are protective compounds against colorectal cancer for both sexes. Prevention of colorectal, mammary, and prostate cancer may also depend on optimal synthesis of the antimitotic prodifferentiating vitamin D hormonal metabolite 1,25-[(OH).sub.2]-cholecalciferol (1,25-D3). Cytochrome-P450-hydroxylases responsible for synthesis (CYP27B1; 25-D3-1[alpha]-hydroxylase) and catabolism (CYP24; 1,25-D3-24-hydroxylase) of 1,25-D3 are not only present in the kidney but are also expressed in human colonocytes, prostate cells, and mammary cells. In addition, levels of CYP27B1, vitamin D receptor, and estrogen receptor-[beta] (the high-affinity receptor for phytoestrogens) are enhanced early during human colorectal cancer, which suggests an interactive physiological defense against tumor progression. We demonstrate in human mammary and prostate cells concentration-dependent regulation of CYP27B1 and of CYP24 by genistein at 0.05-50 [micro]mol/L. The high concentration of 50 [micro]mol/L is very effective in eliminating CYP24 expression in prostate cancer cells. This high concentration can be achieved in vivo in the prostate by an as-yet-unknown concentrative mechanism. Soy feeding, or more effectively genistein feeding, elevates CYP27B1 and reduces CYP24 expression in the mouse colon. In mice fed low nutritional calcium, CYP24 rises in parallel to enhanced colonic proliferation, and genistein counteracts both. We suggest that nutritional soy or genistein can optimize extrarenal 1,25-D3 synthesis, which could result in growth control and, conceivably, in inhibition of tumor progression. KEY WORDS: * extrarenal vitamin D synthesis * extrarenal vitamin D catabolism * estrogen receptor-[beta] * genistein * tumor prevention

The mechanism by which all-trans retinoic acid (ATRA) induces bone resorption is unknown. However, an interaction between vitamin A and vitamin D has been established. In fact, although the mechanism is still unclear, vitamin A has been shown to be a weak antagonist of the actions of vitamin D. Taking into account this interaction and the influence of vitamin D on other calcitropic hormones, such as parathyroid hormone, the effect of vitamin D on ATRA-induced bone resorption was investigated. Vitamin D-deficient rats were fed diets containing 0 or 150 [micro]g of ATRA/g of diet. The rats then were orally administered 0 or 625 ng of cholecalciferol (vitamin [D.sub.3]) daily. Various bone parameters were measured after 3-8 wk. Regardless of the presence or absence of vitamin [D.sub.3], ATRA was able to cause bone resorption. In addition to examining the effect of vitamin D on ATRA-induced bone resorption under normal conditions, this effect also was studied under conditions that inhibit bone mineralization or growth by altering dietary calcium (Ca) and phosphorus (P) levels. Changes in dietary levels of Ca and P did not affect the ability of ATRA to cause bone resorption. Interestingly, despite its ability to stimulate bone resorption, ATRA did not affect serum calcium or phosphorus levels. Overall, the ability of ATRA to cause bone resorption is not dependent on vitamin [D.sub.3], dietary Ca or dietary P. KEY WORDS: * retinoids * osteoclasts * osteoblasts * vitamin A and bone

In the early 1920s, workers in both England and the US had discovered that rats on a rachitic diet would remain healthy if irradiated with ultraviolet light. However, they also found, to their surprise, that 'control' rats too would recover if either their jar was irradiated without the rat in it or if a cage-mate was removed for irradiation and then returned. The ideas that either air or material objects that had been irradiated continued themselves to convey healthful secondary radiations were investigated but not confirmed. There was then the commercially important finding that with irradiation, some rachitic diets would become anti-rachitic. However, this effect did not explain all the previous findings. Consumption of either small irradiated fecal particles or of feces from irradiated rats was the likely explanation for the recovery of nonirradiated rats, but this was not tested by direct experiment, and it now appears unlikely that feces from irradiated rats would show significant antirachitic activity. It is suggested that an alternative possibility - activity of grease from irradiated fur - deserves investigation. Key Words: history; vitamin D; ultraviolet light; irradiation; rachitic diets

Dietary intakes of retinol equivalents, [Alpha]-tocopherol equivalents, vitamin D and phylloquinone were estimated from three sets of 4-d weighed diet records and compared to three corresponding fasting plasma concentrations of retinol, 25-hydroxyvitamin D, [Alpha]-tocopherol, and phylloquinone measured in 34 healthy adults over 20 wk. The magnitude of the correlation between dietary vitamin intake and its corresponding biochemical measure is in part determined by the reproducibility of each of the measures, so within-to-between subject variance ratios were calculated for both dietary intakes and plasma concentrations. Phylloquinone was the only fat-soluble vitamin with a significant correlation between dietary intake and fasting plasma concentration (r = 0.51, P = 0.004). This correlation improved with an increase in both the number of independent diet records and independent plasma measures. Of the dietary intake measures, all the fat-soluble vitamins had greater within than between subject variance, with the highest measured for phylloquinone (6.86:1). Of the plasma measures, only phylloquinone had a within-to-between subject variance ratio greater than one (5.36:1). Comparisons across age and sex for dietary intake and plasma concentrations differed in pattern among the fat-soluble vitamins. KEY WORDS: * vitamin A * vitamin D * vitamin E * vitamin K * humans

Recent studies have identified a heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) as the active complex for mediating positive transcriptional effects of 1,25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2][D.sub.3]], the active hormonal form of vitamin D. The VDR-RXR heterodimer has been shown to bind to direct repeat vitamin D-responsive elements (VDREs) upstream of positively controlled genes in the target tissues for vitamin D, including bone (osteocalcin, osteopontin, and [[Beta].sub.3] integrin), kidney (24-hydroxylase) and intestine (calbindin). Residues that participate in heterodimer formation have been identified in the C-terminal hormone-binding domain by analysis of VDR mutants. The role of the 1,25[(OH).sub.2][D.sub.3] ligand in transcriptional activation by the VDR-RXR heteroclimer is not entirely clear, but studies of two natural VDR mutants suggest that the binding of both hormone and RXR are required to induce a receptor conformation that is competent to activate transcription. A final level of complexity is added by recent observations that VDR is modified by phosphorylation. Thus, the VDR-mediated action of 1,25[(OH).sub.2][D.sub.3] is now known to involve multiple factors that may provide a conceptual basis for future understanding of the tissue-specific genomic effects of 1,25[(OH).sub.2][D.sub.3]. INDEXING KEY WORDS: vitamin D; steroid hormone receptors; transcriptional regulation; heterodimers

Limited data from human observational studies suggest that early supplementation with 10 [micro]g/d (400 IU/d) or less of vitamin D may not reduce the risk for type 1 diabetes but that doses of 50 [micro]g/d (2000 IU/d) and higher may have a strong protective effect. Current U.S. recommendations (5-25 [micro]g/d, 200-1000 IU/d) fall in the largely unstudied dose range in between. All infants and children should receive between 5 [micro]g/d and 25 [micro]g/d of supplemental vitamin D, particularly if they have limited sun exposure, live in northern areas, are exclusively breastfed, or are dark skinned. Caretakers of infants and children at increased risk of type 1 diabetes might wish to consider supplementation toward the upper end of that range or above. Additional studies are needed that 1) investigate the association between 25-hydroxyvitamin D and autoantibodies predictive of type 1 diabetes in infancy and beyond, 2) test the ability of vitamin D supplement doses between 5 and 50 [micro]g/d to prevent autoantibodies and/or type 1 diabetes in infancy and beyond, and 3) examine the safety of vitamin D intakes of 25 [micro]g/d and higher. Also, we need to consider the possible benefits of vitamin D supplementation when deciding whether or not to screen children for type 1 diabetes risk and to add type 1 diabetes to the growing list of outcomes that are considered when vitamin D recommendations are next revised. KEY WORDS: * type I diabetes * autoimmune antibodies * vitamin D infant supplements * 25-hydroxyvitamin D * vitamin D-fortified infant formula * cod-liver oil * and insulin

Vitamin [D.sub.3] supplementation has been reported to inhibit the development of chemically induced colon tumors in young rats fed a high-fat diet. The purpose of this study was to determine whether vitamin [D.sub.3] supplementation would be equally effective in inhibiting aberrant crypt foci (ACF) development in young and adult rats fed a high-fat diet. Young (age 6 wk) and adult (age 49 wk) male F344 rats were given two weekly injections of azoxymethane (15 mg/g) and fed AIN-76; a modified high-fat AIN-76; or a modified high-fat, high-vitamin [D.sub.3] AIN-76. The number and multiplicity of ACF, colonic cell proliferation indexes and serum calcium levels were evaluated after 14 wk. Within each age group there were no differences in the number or multiplicity of ACF observed in the colons of rats fed the different diets (P > 0.05). However, within each diet group, young rats had significantly more ACF with high multiplicity than did adult rats (P < 0.002). Cell proliferation indexes were similar in both age groups and were not altered significantly by the diet treatment. Supplementing a modified high-fat AIN-76 diet with additional vitamin [D.sub.3] at 1 IU/g did not significantly inhibit ACF growth in either young or adult rats. Serum calcium levels were also unaffected by this level of vitamin [D.sub.3] supplementation in both young and adult rats (P > 0.05). In conclusion, higher levels of vitamin [D.sub.3] supplementation in the diet will be required to assess potential age-related differences in the inhibition of colonic cancer development by vitamin [D.sub.3].

Colorectal cancer incidence is reduced in soy-consuming populations. Recent data suggest that the human colon is an estrogen-sensitive organ. Colonocytes express estrogen receptors, and certain phytoestrogens can reduce colonic proliferation in a mouse model. Recently we demonstrated that phytoestrogens regulate the colonic vitamin D system, which could lead to enhanced activation of this autocrine defense against tumor progression. Our model in this study was mice fed AIN76 with or without 20% soy meal. In other experimental groups, AIN76 was supplemented with 0.04% genistein and normal (0.5%) or low (0.04%) calcium. Our rationale was that positive effects of phytoestrogens on the vitamin D system become visible mainly when mucosal cells are induced to hyperproliferate by low calcium in the diet. Methods used were real time RT-PCR, semiquantitative PCR, and immunoblotting. Our data demonstrated gender- and segment-specific action of soy. The vitamin D receptor was modulated only in males and only in the right-side colon. This was paralleled by increased activation of caspase 3, a marker for enhanced apoptosis. Soy downregulated CYP24, the vitamin D-catabolizing hydroxylase, again mainly in the male and in the right-side colon. CYP24 was extremely low in the distal colon. There was no significant change in CYP27B1, the vitamin D-synthesizing hydroxylase, neither gender- nor segment-specific. Results from genistein-treated groups indicated that this substance was even more effective than soy: when hyperproliferation was induced in the mouse colon by feeding AIN76 containing 0.04% calcium, CYP24 increased dramatically, but genistein feeding reduced expression to control levels whereas CYP27B1 levels were increased. Our data showed that soy and genistein indeed regulate the colonic vitamin D system and, in parallel, also regulate proliferation and apoptosis in a direction that might be inhibitory for progression of colonic premalignancy. Interestingly, males appear to be affected more favorably than females. [Supported by a grant from the American Institute for Cancer Research, Washington, DC.]

BACKGROUND. Vitamin D has been shown to promote differentiation of cells and inhibit growth in many cancer cells through its effects on nuclear receptors, but it has also been proposed that there may be nonreceptor-mediated effects on cellular function. We investigated the effects of vitamin D on two human colon cancer cell lines obtained from the same patient at early and metastatic stages with and without vitamin D receptor (VDR) and 1-[alpha]-vitamin D hydroxylase activity (1-[alpha]-VD-OHase), respectively. METHODS. Cell lines SW480 (primary colon cancer) and SW620 (metastatic lesion from the same patient) were obtained from the American Type Culture Collection and grown under standard conditions. RNA was extracted by RNeasy Total Isolation Kit (QIAGEN). Reverse-transcription polymerase chain (RT-PCR) reaction was performed by the Superscript Choice System (Gibco BRL). Cells were synchronized by 24-h depletion of fetal bovine serum. Approximately 30,000 cells/well were plated on 6-well Falcon plastic tissue culture dishes. Vitamin D was added to the culture media at concentrations ranging from 10 pmol/L to 10 [micro]mol/L at day of seeding (day 0). Cells were counted by hemocytometer by two observers blinded to treatment every 24 h until a growth curve demonstrated maximal inhibition. The Student's t test was used to assess statistical significance between treated and control groups. RESULTS. RT-PCR results confirmed that the SW480 cell line is [VDR.sub.+] and 1-[alpha]-VD-[OHase.sub.+] whereas the SW620 cell line is [VDR.sub.-] and 1-[alpha]-VD-[OHase.sup.-]. Vitamin D had dose-dependent antiproliferative effects on both cell lines. There was a 67% decrease in growth in the SW480 cell line (P < 0.05) and a 41% decrease in growth in the SW620 cell line (P < 0.05) after 5 d of VD treatment compared with untreated cells. DISCUSSION. These results suggest that the antiproliferative effects mediated by vitamin D may be independent of the VDR because antiproliferation was observed in the cell line lacking the VDR. Alternatively, incubating [VDR.sub.-] cell lines with vitamin D may result in VDR induction. [Supported by National Institutes of Health grant 42710.]