Production of 1,25-dihydroxyvitamin D3 by human T cell lymphotrophic virus-I-transformed lymphocytes.

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Abstract

The human T cell lymphotrophic virus type I (HTLV-I) has recently been identified in a T cell lymphoma associated with hypercalcemia and increased bone turnover. Since increased serum concentrations of 1,25-dihydroxyvitamin D have been reported in this disease, we have examined the capacity of HTLV-I-infected cord blood lymphocytes to metabolize 25-hydroxyvitamin D3. Our results demonstrate that HTLV-I-infected cells have the capacity to metabolize 25-hydroxyvitamin D3 to a substance that co-migrates with 1,25-dihydroxyvitamin D3 by high performance liquid chromatography over a silica column using either 12% isopropanol in hexane or 5% isopropanol in dichloromethane. The metabolite binds to the 1,25-dihydroxyvitamin D3 receptor in rat osteosarcoma cells and stimulates bone resorption in cultures of fetal rat long bones. Mass spectrometric analysis of the metabolite confirmed the presence of 1,25-dihydroxyvitamin D3. Production of 1,25-dihydroxyvitamin D by lymphoma cells may contribute to the pathogenesis of the hypercalcemia seen in patients with HTLV-I-associated T cell lymphomas.

Authors

D A Fetchick, D R Bertolini, P S Sarin, S T Weintraub, G R Mundy, J F Dunn