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25-Hydroxyvitamin D3 Metabolism by Human T-Lymphotropic Virus-Transformed Lymphocytes^*

HELMUT REICHEL, H. PHILLIP KOEFFLER and ANTHONY W. NORMAN

Division of Biomedical Sciences, Department of Biochemistry, University of California Riverside, California 92521
The Division of Hematology, Department of Medicine, University of California (H.P.K.) Los Angeles, California 90024

Address all correspondence and requests for reprints to: Prof. Anthony W. Norman, Department of Biochemistry, University of California, Riverside, California 92521.

Production of 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] by human T-lymphotropic virus-I (HTLV-I)-infected lymphocytes may be the cause of the hypercalcemia frequently found in HTLV-I-associated adult T-cell lymphoma/leukemia. We examined three HTLV-I-transformed lymphocyte cell lines, two HTLV-II-transformed lymphocyte cell lines, and six HTLV-negative B and T-lymphocyte leukemia cell lines for metabolism of 25-hydroxyvitamin D₃ (25OHD₃). One HTLV-I-positive cell line, designated S-LB1, converted the substrate 25OH-[³H]D₃ to several more polar metabolites, which were identified by high performance liquid chromatographic analysis as putative 1,25-(OH)₂D₃, 24,25-dihydroxyvitamin D₃ [24,25-(OH)₂D₃], and 1,24,25-trihydroxyvitamin D₃ [1,24,25-(OH)₃D₃]. The other cell lines gave no evidence of 25OH-[₃H]D₃ metabolism. Likewise, phytohemagglutinin-stimulated normal human lymphocytes did not metabolize 25OH-[³H]D₃. The characteristics of 25OHD₃ metabolism by S-LB1 cells were investigated in more detail. Kinetic studies revealed average K_m values of 92 and 383 nM for 25OHD₃ 1-hydroxylase and 24-hydroxylase, respectively. Time-course studies showed that both 1,25-(OH)₂-[³H]D₃ and 24,25-(OH)₂-[³H]D₃ were further metabolized by S-LBl cells to more polar compounds [primarily 1,24,25-(OH)₃D₃] and to compounds from which part of the side-chain had been cleaved. Exogenous 1,25-(OH)₂D₃ (1) inhibited endogenous 1,25-(OH)₂D₃ production, (2) stimulated 24,25-(OH)₂D₃ production, and (3) stimulated production of compounds more polar than 1,25-(OH)₂D₃. Bovine PTH-(1–34) had no effect on 25OH-[³H]D₃ metabolism by S-LBl cells. Our results indicate that the 25OH-[³H]D₃-metabolizing system of cultured HTLV-I-transformed S-LBl lymphocytes is similar but not identical to that of kidney cell culture systems. It appears, however, that infection of lymphocytes with HTLV does not uniformly result in acquisition of the competence to metabolize 25OHD₃.

^* This work was supported by USPHS Grants AM-14-750-016, CA 26038, CA-33936, and CA-3273.

Fellow of the Deutsche Forschungsgemeinschaft (Re 613/1-2).

Received March 16, 1987.