CONSTITUTIVE SYNTHESIS OF 1,25-DIHYDROXYVITAMIN D-3 BY A HUMAN SMALL-CELL LUNG-CANCER CELL-LINE

One of 16 human small cell lung cancer cell lines examined was shown t o synthesize a metabolite resembling 1,25-dihydroxyvitamin D-3 [1,25-( OH)(2)D-3]. The NCl H82 line converted 25-hydroxyvitamin D-3 (25OHD(3) ) into a compound indistinguishable from 1,25-(OH)(2)D-3 in 3 differen t high performance liquid chromatography systems. Electron impact mass spectra for the trimethylsilylethers of the metabolite and authentic 1,25-(OH)(2)D-3 were indistinguishable. Binding to an anti-1,25-(OH)(2 )D-3 antibody was identical for the metabolite and authentic 1,25-(OH) (2)D-3, whereas administration to rats in. vivo caused equivalent stim ulation of calcium transport measured in vitro in duodenal sacs. Activ ity of the H82 1 alpha-hydroxylase appears to be substrate dependent a nd is not stimulated by PTH, suggesting that it is similar to the enzy me expressed by activated macrophages and other cell types at extraren al sites. Inhibition by ketoconazole indicates that, like the renal an d extrarenal enzymes, the H82 enzyme is cytochrome P450 dependent. The se data indicate that the H82 small cell lung cancer cell line constit utively expresses 25-hydroxyvitamin D-3-1 alpha-hydroxylase and can sy nthesize 1,25-(OH)(2)D-3.