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E Abe

Publications and source records attributed to E Abe.

At least 145 records · Page 8Linked to original sources
PubMed1986

Differentiation-inducing factor purified from conditioned medium of mitogen-treated spleen cell cultures stimulates bone resorption.

Spleen cells treated with mitogens produce a potent bone-resorbing factor called osteoclast-activating factor (OAF). To examine the relationship between the bone-resorbing factor and other protein factors produced by spleen cells, the colony-stimulating factor (CSF), the differentiation-inducing factor (DIF), the macrophage fusion factor (MFF), and the macrophage growth factor (MGF) were purified from 2.68 liters of conditioned medium of mouse spleen cell cultures treated with concanavalin A. Purification was performed successively by DEAE-cellulose, Blue Sepharose, and Sephadex G-150 column chromatography and high-pressure liquid chromatography (HPLC). The DIF was successfully separated from CSF and MGF on HPLC. CSF coincided with MGF on HPLC, but MFF disappeared before application to HPLC. Only the DIF exhibited bone-resorbing activity, whereas CSF and MGF did not. The DIFs purified from L929 cells and Ehrlich ascites tumors similarly exhibited bone-resorbing activity. The DIFs purified from spleen cells and Ehrlich ascites tumor cells exhibited neither interleukin 1 (IL-1) activity nor tumor necrosis factor (TNF) activity, though the unfractionated conditioned medium from spleen cells did exhibit them. In the light of recent reports that IL-1 beta and TNF also stimulate bone resorption, the term OAF should refer to a generic activity rather than a single factor.

Animals↗
PubMed1986

Enhancement by 1 alpha,25-dihydroxyvitamin D3 of chemically induced transformation of BALB 3T3 cells without induction of ornithine decarboxylase or activation of protein kinase C1.

We reported previously that 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonally active form of vitamin D3, markedly enhanced methylcholanthrene-induced transformation of BALB 3T3 A31-1-1 cells. When the cells were treated with methylcholanthrene (1 microgram/ml) for 72 h and then with 1 alpha,25(OH)2D3 (5 ng/ml) for 2 wk, the transformation frequency was 1.95 +/- 0.73 (SD) foci/dish in 8 independent experiments, which was about 20 times that in cultures treated with methylcholanthrene only. Even at a physiological concentration in plasma, i.e., 0.05 ng/ml, 1 alpha,25(OH)2D3 enhanced the transformation frequency significantly (P less than 0.001). 1 alpha,25(OH)2D3 was not cytotoxic but slightly inhibited growth of the cells. Cells treated with 1 alpha,25(OH)2D3 were thin and became arranged in a meshwork with wide intercellular spaces. These morphological changes were reversible. 1 alpha,25(OH)2D3 induced DNA synthesis in quiescent BALB 3T3 cells dose and time dependently, but this effect was less than that of 12-O-tetradecanoylphorbol-13-acetate. Unlike 12-O-tetradecanoylphorbol-13-acetate, 1 alpha,25(OH)2D3 did not interfere with the binding of epidermal growth factor or phorbol dibutyrate. 1 alpha,25(OH)2D3 did not induce ornithine decarboxylase. Moreover, it did not activate protein kinase C in quiescent BALB 3T3 cells or this enzyme isolated from mouse brain. BALB 3T3 cells and their transformants contain a specific cytosol receptor for 1 alpha,25(OH)2D3, but the binding sites of the transformants were fewer and had lower affinity than those of untransformed BALB 3T3 cells. These effects of 1 alpha,25(OH)2D3 were specific, because other derivatives of vitamin D3 induced the same effects only at 200 times or more higher concentrations.

Animals↗
PubMed1986

Induction of anchorage-independent growth of JB6 mouse epidermal cells by 1 alpha,25-dihydroxyvitamin D3.

1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonally active form of vitamin D3, was shown previously to enhance chemically induced transformation of BALB 3T3 cells and Syrian hamster embryo cells. This report demonstrates that 1 alpha,25(OH)2D3, like phorbol ester tumor promoters, induces anchorage-independent growth of mouse JB6 epidermal cells. When plated on agar plates containing 1 alpha,25(OH)2D3 at concentrations higher than 0.05 ng/ml or 0.12 nM, JB6 cells formed colonies on the surface of agar plates dose dependently. This anchorage-independent growth was further confirmed by stimulation of DNA synthesis after liquefying the agar layer with NaI. A phorbol-ester resistant variant of JB6 cells was also resistant to 1 alpha,25(OH)2D3 in terms of induction of anchorage independency. Induction of anchorage-independent growth was specific for 1 alpha,25(OH)2D3: other derivatives of vitamin D3 also induced colony formation on agar plates but only at a higher concentration (500 ng/ml) and to much less extent than did 1 alpha,25(OH)2D3. JB6 cells were found to contain a receptor specific for 1 alpha,25(OH)2D3 with a Kd of 55.7 pM and Nmax of 102.5 fmol/mg protein, suggesting a receptor-mediated mechanism of the induction. The clone that was resistant to 1 alpha,25(OH)2D3 also contained the receptor. DNA-cellulose chromatography showed that a 1 alpha,25(OH)2D3-receptor complex interacted with DNA. In contrast to 1 alpha,25(OH)2D3, retinoic acid did not induce anchorage-independent growth of JB6 cells, but it inhibited the induction by 1 alpha,25(OH)2D3 when applied with it.

Animals↗
PubMed1985

Syntheses and differentiating action of vitamin D endoperoxides. Singlet oxygen adducts of vitamin D derivatives in human myeloid leukemia cells (HL-60).

Singlet oxygen adducts of various vitamin D derivatives, 6,19-dihydro-6,19-epidioxyvitamin D (vitamin D endoperoxides, 2 and 2'), were chemically synthesized, and their biological activity in inducing differentiation of a human myeloid leukemia cell line (HL-60 cells) was examined. The potency of the endoperoxides derived from vitamin D derivatives possessing the 1 alpha-hydroxyl group such as 1 alpha, 25-dihydroxyvitamin D3 endoperoxides (2b and 2b') was markedly (10(-2)) diminished relative to the respective parent vitamin D compounds. In contrast, 25-hydroxyvitamin D3 endoperoxides [25-(OH)D3 endoperoxides, 2a and 2a'] and their analogues fluorinated at the 24- or 26- and 27-positions were 2.5-10 times more potent than 25-hydroxyvitamin D3 (1a) in spite of the absence of the conjugated triene structure typical of vitamin D compounds. The potency of these vitamin D endoperoxides (2 and 2'), especially those lacking the 1 alpha-hydroxyl group, in inducing differentiation of HL-60 cells was not correlated with their activity in binding to the cytosol receptor for 1 alpha, 25-dihydroxyvitamin D3 (1b). The binding efficiency to the receptor was relatively lower than the differentiating activity. To examine the action of vitamin D endoperoxides, carbon analogues of 25-(OH)D3 endoperoxides, two C-6 epimers of 25-hydroxy-6,19-dihydro-6,19-ethanovitamin D3 (6 and 6'), were synthesized. The carbon analogues (6 and 6') had no potential to induce differentiation of HL-60 cells. These results suggest that vitamin D endoperoxides (2 and 2') express their biological activity probably after being converted to some other compounds.

Binding, Competitive↗
PubMed1985

Mechanism of the differentiating action of 25-hydroxyvitamin D3 endoperoxides in human myeloid leukemia cells (HL-60).

The action of 25-hydroxy-6,19-dihydro-6,19-epidioxyvitamin D3 [25-(OH)D3 endoperoxides, 2a and 3a] in inducing differentiation of human myeloid leukemia cells (HL-60) was studied by using their radioactive derivatives (2a' and 3a'). When HL-60 cells were incubated with the labeled endoperoxides (2a' and 3a') in serum-free RPMI 1640 medium, no radioactivity was incorporated into either the cytosol or the chromatin fraction of the cells. When the radioactive endoperoxide (2a') was incubated in the culture medium for 3 days, with or without HL-60 cells, about 45% of the compound was similarly converted to 19,25-dihydroxy-6,19-dihydro-6,19-epoxyvitamin D3 (4a) and about 10% to 25-hydroxy-6,19-epoxyvitamin D3 (6a). These two new vitamin D derivatives were synthesized chemically and tested for their biological activities. Both compounds (4a and 6a) were about 2 times as active as 25-(OH)D3 endoperoxides (2a and 3a) and about 7 times as active as 25-hydroxyvitamin D3 (1a) in inducing differentiation of HL-60 cells. The differentiating activity of these compounds was well correlated with their activity in binding to the cytosol receptor for 1 alpha, 25-dihydroxyvitamin D3 in HL-60 cells. The in vitro bone-resorbing activity of 25-hydroxy-6,19-epoxyvitamin D3 (6a) and 25-(OH)D3 endoperoxide (2a) was higher than that of 25-hydroxyvitamin D3 (1a), indicating that the differentiating activity also paralleled the bone-resorbing activity in these vitamin D derivatives. These results suggest that 25-(OH)D3 endoperoxides (2a and 3a) induce differentiation of HL-60 cells and bone resorption after being converted to these two compounds.

Animals↗
PubMed1985

Regulation of melanin synthesis of B16 mouse melanoma cells by 1 alpha, 25-dihydroxyvitamin D3 and retinoic acid.

Melanin synthesis of B16 mouse melanoma cells was found to be stimulated dose and time dependently by 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the hormonal form of vitamin D3. The stimulation of melanogenesis resulted from an increase in the activity of tyrosinase, a key enzyme in melanin synthesis. The minimum dose required for this stimulation was as low as 0.05 ng/ml, or 0.12 nM, a physiological level of plasma 1 alpha,25(OH)2D3. The stimulation by 1 alpha,25(OH)2D3 was specific; other derivatives of vitamin D3 caused no stimulation at a concentration of 500 ng/ml. When the cells were plated on agar plates, the proportion of dark or black colonies was not increased by the exposure to 1 alpha,25(OH)2D3. Furthermore, this compound did not induce melanin synthesis of an amelanotic variant. Thus, its stimulatory effect seemed to be due to stimulation of melanin synthesis of melanotic cells, rather than to conversion of amelanotic clones to melanotic ones. 1 alpha,25(OH)2D3 did not induce intracellular cyclic adenosine 3':5'-monophosphate, while cholera toxin induced cyclic adenosine 3':5'-monophosphate and stimulated melanin synthesis and tyrosinase activity much more than did 1 alpha,25(OH)2D3, suggesting that 1 alpha,25(OH)2D3 stimulates melanin synthesis by a cyclic adenosine 3':5'-monophosphate-independent mechanism. B16 melanoma cells contained specific receptors for 1 alpha,25(OH)2D3. Scatchard plot analysis revealed two types of receptor; the high-affinity receptor had a Kd of 18.3 pM and an Nmax of 10.6 fmol/mg of protein. The specificity of receptor binding was demonstrated by studies showing that, for 50% displacement of 1 alpha,alpha,25(OH)2D3 binding, other derivatives were required at 500 times higher concentrations or more. In contrast to 1 alpha,25(OH)2D3, retinoic acid inhibited melanin synthesis and tyrosinase activity of B16 melanoma cells dose and time dependently. On simultaneous treatment, 1 alpha,25(OH)2D3 and retinoic acid caused mutual interference, and a balance between their respective stimulating and inhibitory effects was obtained at a molar ratio of 10:1; i.e., with 10 nM 1 alpha,25(OH)2D3 and 1 nM retinoic acid.

Animals↗
PubMed1985

Alternative differentiation of human promyelocytic leukemia cells (HL-60) induced selectively by retinoic acid and 1 alpha,25-dihydroxyvitamin D3.

Induction of hematopoietic differentiation was investigated in human promyelocytic leukemia cells [HL-60] using two lipophilic vitamins, retinoic acid and 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3]. Both vitamins suppressed proliferation and induced differentiation of HL-60 cells, but 1 alpha,25(OH)2D3 was 70- to 100-fold more potent than was retinoic acid on a molar basis. Simultaneous treatment with suboptimal concentrations of 1 alpha,25(OH)2D3 (0.12 to 1.2 nM) and retinoic acid (10 to 100 nM) showed additive effects in reducing nitroblue tetrazolium, a common marker for monocyte-macrophage and granulocyte differentiation. For the study of alternative differentiation of the cells by the two vitamins, we used monoclonal antibodies specific for either human monocyte-macrophages or granulocytes and other markers specific for macrophage differentiation such as alpha-naphthyl acetate esterase activity and adherence to the dish surface. HL-60 cells were induced to differentiate alternatively into macrophages by 1 alpha,25(OH)2D3 or into granulocytes by retinoic acid. When HL-60 cells were treated with various concentrations of 1 alpha,25(OH)2D3 (1.2 to 120 nM) in the presence of 1000 nM retinoic acid which is a concentration sufficient to induce maximal granulocyte differentiation, the appearance of the markers for monocyte-macrophage differentiation by 1 alpha,25(OH)2D3 was not at all affected by the retinoic acid. These results indicate that 1 alpha,25(OH)2D3 and retinoic acid have additive effects in inducing differentiation of HL-60 cells, but monocyte-macrophage differentiation by 1 alpha,25(OH)2D3 occurs much more readily than does granulocyte differentiation by retinoic acid.

Calcitriol↗
PubMed1985

[Present status and characteristics of the terminal care of dying patients in head and neck cancer].

Sixty-two head and neck cancer patients who died in 1981 and 1982 were analyzed. At the terminal stage, most of the patients could see or feel their tumors by themselves. Seventy-one percent of them were laryngectomized or tracheotomized, so they could not speak, and its was frequently difficult to know what they wanted to say or ask. These 2 facts made the clinical care of these patients difficult. More than half of the families of these patients did not want them to live longer only to be tortured by their disease.

Adolescent↗
PubMed1984

1 alpha, 25-Dihydroxyvitamin D3 directly induces fusion of alveolar macrophages by a mechanism involving RNA and protein synthesis, but not DNA synthesis.

The results of our present study indicate that 1 alpha, 25-dihydroxyvitamin D3[1 alpha, 25(OH)2D3] directly induces fusion of mouse alveolar macrophages without any participation of T-lymphocytes by a mechanism involving RNA and protein synthesis but not DNA synthesis. We have reported that 1 alpha, 25(OH)2D3 induces fusion of alveolar macrophages by a direct mechanism and by a spleen cell-mediated indirect mechanism [(1983) Proc. Natl. Acad. Sci. USA 80, 5583-5587]. Alveolar macrophages pretreated with or without anti-Thy 1.2 antibody and complement fused similarly when they were incubated with 1 alpha, 25(OH)2D3. The vitamin suppressed DNA synthesis, but it significantly enhanced RNA and protein synthesis. The 1 alpha, 25(OH)2D3-induced fusion was blocked by adding actinomycin D or cycloheximide, but not by hydroxyurea.

Animals↗
PubMed1984

Inhibition by 1 alpha,25-dihydroxyvitamin D3 of dimethyl sulfoxide-induced differentiation of Friend erythroleukemia cells.

Regulation of erythroid differentiation by vitamin D3 derivatives was examined in Friend erythroleukemia cells. After Friend cells were cultured for 5 days with 1.5% dimethyl sulfoxide (DMSO), as much as 70% of the cells became benzidine-positive and the hemoglobin content increased in parallel with the increase of benzidine-positive cells. The DMSO-induced erythroid differentiation was markedly inhibited by concurrent addition of the active form of vitamin D3, 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3]. Of the vitamin D3 derivatives tested, 1 alpha,25(OH)2D3 was the most potent in inhibiting DMSO-induced erythroid differentiation. 1 alpha,25(OH)2D3 alone was totally ineffective in both cell growth and erythroid differentiation. These results together with our previous reports indicate that 1 alpha,25(OH)2D3 is somehow involved not only in myeloid differentiation, but also in erythroid differentiation.

Animals↗
PubMed1984

Activation and fusion induced by 1 alpha,25-dihydroxyvitamin D3 and their relation in alveolar macrophages.

1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] induces fusion of murine alveolar macrophages. This effect was observed in growth medium containing 5% human serum but not in the medium with 5% fetal bovine serum. Unlike 1 alpha,25-(OH)2D3, bacterial lipopolysaccharides (LPS) did not induce fusion of alveolar macrophages. However, both 1 alpha,25-(OH)2D3 and LPS activated alveolar macrophages, as measured by glucose consumption, increase in Fc receptors, and induction of cytotoxicity. The number of Fc receptors on the surface of multinucleated giant cells induced by 1 alpha,25-(OH)2D3 was much smaller than that on the surface of mononuclear macrophages treated with the hormone. These results indicate that 1 alpha,25-(OH)2D3 induces both fusion and activation of alveolar macrophages, whereas LPS elicits activation only.

Animals↗
PubMed1984

Extracellular calcium is involved in the mechanism of differentiation of mouse myeloid leukemia cells (M1) induced by 1 alpha, 25-dihydroxyvitamin D3.

We have reported that 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3] suppresses proliferation and induces differentiation of murine myeloid leukemia cells (M1) into macrophages. In the current study, M1 cells were cultured either with 2.0 or 0.15 mM total calcium to examine the effect of calcium on the process of differentiation induced by the vitamin. The 0.15 mM calcium medium greatly enhanced 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3]-induced inhibition of cell growth and suppression of [3H]thymidine incorporation. Addition of Verapamil, a calcium antagonist, to the 2.0 mM calcium medium also elicited similar responses. The absolute number of cells with phagocytic activity induced by 1 alpha, 25(OH)2D3 was almost identical in media containing either concentration of calcium, and in cultures with or without Verapamil. Culture in the 0.15 mM calcium medium or addition of Verapamil to the 2.0 mM calcium medium did not suppress cell growth nor induce phagocytic activity in the absence of the vitamin. To confirm the preferential effect of calcium on cell growth, M1 cells were pretreated for 3 days with 1 alpha, 25(OH)2D3 in either the 2.0 or 0.15 mM calcium medium. Then the pretreated cells were washed and subcultured in the absence of 1 alpha, 25(OH)2D3 in either medium. The growth rate was inhibited much more effectively in the subculture with 0.15 mM calcium than with 2.0 mM calcium. These results suggest that the M1 cells' increased requirement of extracellular calcium, caused by the treatment with 1 alpha, 25(OH)2D3, is closely related to cell growth rather than differentiation.

Animals↗
PubMed1983

1 alpha,25-dihydroxyvitamin D3 induces differentiation of human promyelocytic leukemia cells (HL-60) into monocyte-macrophages, but not into granulocytes.

The differentiating action of 1 alpha,25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3] in hematopoietic cells was examined in 3 tumor cell lines. 1 alpha,25-(OH)2D3 induced common differentiation-associated properties in macrophages and granulocytes similarly in mouse myeloblastic leukemia cells (M1), human promyelocytic leukemia cells (HL-60) and human histiocytic monoblast-like lymphoma cells (U937). 1 alpha,25(OH)2D3 markedly induced alpha-naphthyl acetate esterase activity, a typical marker of monocyte-macrophages, in M1 and HL-60 cells. In HL-60 and U937 cells, the vitamin also induced binding of the monoclonal antibody MAS 072, specific for monocyte-macrophages, but not of MAS 067, specific for granulocytes. These results clearly indicate that 1 alpha, 25(OH)2D3 induces differentiation of all cell lines examined preferentially along the monocyte-macrophage pathway.

Calcitriol↗
PubMed1983

The role of vitamin D in the medullary bone formation in egg-laying Japanese quail and in immature male chicks treated with sex hormones.

The effect of vitamin D3 on medullary bone formation was investigated in egg-laying Japanese quail and in immature male chicks treated with sex hormones. When laying quail were fed a vitamin D-deficient diet for 16 days, their eggshell weights and egg production rate were markedly reduced in a time-dependent manner with a significant decrease in plasma calcium and 25-hydroxyvitamin D3 levels. The calcium content of the medullary bone of femurs decreased markedly with the progress of vitamin D deficiency, whereas that of the cortical bone remained unchanged. Quantitative histological examination also showed that the area of the mineralized portion of medullary bone in quail that were fed the vitamin D-deficient diet markedly decreased compared with that in the control laying quail, whereas the total area of the mineralized and unmineralized portions of medullary bone in the bone marrow cavity increased moderately. Daily administration of vitamin D3 (0.75 microgram/day) to the vitamin D-deficient quail increased the mineralization of medullary bone as early as day 4. Daily administration of both estradiol (0.3 mg/day) and testosterone (0.9 mg/day) for 3 weeks to immature male chicks induced an apparent hypercalcemia and matrix formation of medullary bone, regardless of the vitamin D status of the chicks. Mineralization of medullary bone was observed only when vitamin D3 was administered together with the sex hormones. These results suggest that vitamin D3 is directly involved in the mineralization of medullary bone in birds.

Animals↗
PubMed1983

Biological activity of 24,24-difluoro-1 alpha, 25-dihydroxyvitamin D3 and 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone in inducing differentiation of human myeloid leukemia cells.

Vitamin D compounds added to the culture medium induce differentiation of human myeloid leukemia cells (HL-60 cells) by binding to a specific cytosol receptor protein. This system provides a biologically relevant and technically simple assay to examine the relationship between molecular structure and biological activity of vitamin D compounds. Using this culture system, the biological activity of 24,24-F2-1 alpha,25(OH)2D3 and 1 alpha,25(OH)2D3-26,23-lactone was assayed. 24,24-F2-1 alpha,25(OH)2D3 was four to seven times more potent than 1 alpha,25(OH)2D3 in inducing phagocytosis and C3 rosette formation of HL-60 cells, though both compounds bound equally well to the cytosol receptor, suggesting that the defuorination at the 24-carbon position may stimulate membrane permeability of the compound. 1 alpha,25(OH)2D3-26,23-lactone, on the other hand, was only 1/200th as active as 1 alpha,25(OH)2D3. The binding affinity of the lactone for the cytosol receptor was identical with that of 1 alpha (OH)D3, suggesting that the lactone formation between the 26 and 23 positions masks the function of the 25-hydroxyl group. The binding affinity of vitamin D3 derivatives to the specific cytosol receptor of HL-60 cells was well correlated with that of intestinal cytosol protein specifically bound to 1 alpha,25(OH)2D3.

Calcitriol↗
PubMed1983

Cooperative effect of 1 alpha,25-dihydroxyvitamin D3 and dexamethasone in inducing differentiation of mouse myeloid leukemia cells.

Murine myeloid leukemia cells (MI) are induced to differentiate into macrophages by the metabolically active form of vitamin D3,1 alpha,25-dihydroxyvitamin D3[1 alpha,25(OH)2D3] (E. Abe et al., (1981) Proc. Natl. Acad. Sci. USA 78, 4990-4994). At 0.12-120 nM, 1 alpha,25(OH)2D3 suppressed cell growth in a dose-dependent manner and markedly induced phagocytic activity, lysozyme activity, and C3-receptor formation. The potency of 1 alpha,25(OH)2D3, at 0.12-120 nM, in inducing differentiation was nearly equivalent to that of 10-10,000 nM of dexamethasone, one of the most potent stimulators of Ml cells. Simultaneous treatment with low physiological plasma concentrations of 1 alpha,25(OH)2D3 (0.12 nM) and dexamethasone (10 nM) induced differentiation of Ml cells equivalent to the responses obtained only by using much higher concentrations of the respective steroids when used separately. In addition, two variant clones of Ml cells resistant to either 1 alpha,25(OH)2D3 or dexamethasone were isolated. One was resistant to 120 nM of 1 alpha,25(OH)2D3 but sensitive to 10-1000 nM of dexamethasone. The other was resistant to 1000 nM of dexamethasone but sensitive to 12 nM of 1 alpha,25(OH)2D3. This suggests that the mechanism of action of 1 alpha,25(OH)2D3 in inducing differentiation of Ml cells is different at least in part from that of dexamethasone, and that combination therapy by both steroids may be useful in reducing leukemogenicity of Ml cells in vivo.

Animals↗
PubMed1983

1 alpha,25-Dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 prolong survival time of mice inoculated with myeloid leukemia cells.

Syngeneic SL mice inoculated with murine myeloid leukemia cells (M1) all died of leukemia within 30 days. Treatment three times a week with 12.5-50 pmol per mouse of either 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the active form of vitamin D3, or its synthetic analog, 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3], considerably prolonged the survival time of mice inoculated with M1 cells. 1 alpha(OH)D3 was more effective than 1 alpha,25(OH)2D3 in increasing the survival time of the mice. 1 alpha(OH)D3 also increased the survival time of nude mice inoculated with M1 cells. The 1 alpha(OH)[3H]D3 administered intraperitoneally to tumor-bearing mice was converted very rapidly to 1 alpha,25(OH)2-[3H]D3. The chronic administration of 25 pmol of 1 alpha(OH)D3 to tumor-bearing mice for 30 days caused no appreciable hypercalcemia. These results indicate clearly that 1 alpha,25(OH)2D3 is effective not only in inducing differentiation of M1 cells in vitro, as previously reported [Abe, E., Miyaura, C., Sakagami, H., Takeda, M., Konno, K., Yamazaki, T., Yoshiki, S. & Suda, T. (1981) Proc. Natl. Acad. Sci. USA 78, 4990-4994], but also in prolonging the survival time of mice inoculated with M1 cells.

Animals↗