Mawer E B, Hayes M E, Heys S E, Davies M, White A, Stewart M F, Smith G N
Manchester University Bone Disease Research Center, United Kingdom.
J Clin Endocrinol Metab. 1994 Aug;79(2):554-60. doi: 10.1210/jcem.79.2.8045976.
One of 16 human small cell lung cancer cell lines examined was shown to synthesize a metabolite resembling 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. The NCI H82 line converted 25-hydroxyvitamin D3 (25OHD3) into a compound indistinguishable from 1,25-(OH)2D3 in 3 different high performance liquid chromatography systems. Electron impact mass spectra for the trimethylsilylethers of the metabolite and authentic 1,25-(OH)2D3 were indistinguishable. Binding to an anti-1,25-(OH)2D3 antibody was identical for the metabolite and authentic 1,25-(OH)2D3, whereas administration to rats in vivo caused equivalent stimulation of calcium transport measured in vitro in duodenal sacs. Activity of the H82 1 alpha-hydroxylase appears to be substrate dependent and is not stimulated by PTH, suggesting that it is similar to the enzyme expressed by activated macrophages and other cell types at extrarenal sites. Inhibition by ketoconazole indicates that, like the renal and extrarenal enzymes, the H82 enzyme is cytochrome P450 dependent. These data indicate that the H82 small cell lung cancer cell line constitutively expresses 25-hydroxyvitamin D3-1 alpha-hydroxylase and can synthesize 1,25-(OH)2D3.
在检测的16种人小细胞肺癌细胞系中，有1种被证明能合成一种类似于1,25 - 二羟维生素D3 [1,25-(OH)2D3]的代谢物。NCI H82细胞系在3种不同的高效液相色谱系统中，能将25 - 羟维生素D3（25OHD3）转化为一种与1,25-(OH)2D3无法区分的化合物。该代谢物和 authentic 1,25-(OH)2D3的三甲基硅醚的电子轰击质谱无法区分。该代谢物与 authentic 1,25-(OH)2D3与抗1,25-(OH)2D3抗体的结合情况相同，而在体内给予大鼠时，对十二指肠囊体外测量的钙转运有同等程度的刺激。H82 1α - 羟化酶的活性似乎依赖于底物，且不受甲状旁腺激素（PTH）刺激，这表明它类似于肾外部位活化巨噬细胞和其他细胞类型所表达的酶。酮康唑的抑制作用表明，与肾和肾外的酶一样，H82酶依赖细胞色素P450。这些数据表明，H82小细胞肺癌细胞系组成性地表达25 - 羟维生素D3 - 1α - 羟化酶，并能合成1,25-(OH)2D3。
