ORNITHINE DECARBOXYLASE AND POLYAMINE LEVELS IN COLUMNAR UPPER GASTROINTESTINAL MUCOSAE IN PATIENTS WITH BARRETTS ESOPHAGUS

  • 1 June 1988
    • journal article
    • research article
    • Vol. 48  (11) , 3288-3291
Abstract
Ornithine decarboxylase (ODC) activity was elevated in the premalinant metaplastic columnar epithelium (mean activity, 0.13 unit/mg protein, N = 18 individual samples from 18 patients), compared to their adjacent gastric (mean activity, 0.02 unit/mg protein, N = 9) or small intestional (mean activity, 0.02 unit/mg protein, N = 9) epithelium in patients with Barret''s esophagus. Enzyme activity ranged from 0 (less than detectable) to more than 0.5 unit/mg protein in the metaplastic tissue. However, neither putrescine, spermidine, spermine (as individual parameters), nor total polyamine contents were related to ODC activity in the individual patient biopsies. Spermidine/spermine ratios ranged from 0.38 to 2.18 and were also not related to enzyme activity in any apparent manner. Nevertheless, cell strains derived from the metaplastic tissue were growth inhibited by .alpha.-difluoromethylornithine, an enzyme-activated, suicide inhibitor of ODC. In two different cell strains derived from Barrett''s epithelium, growth was affected with drug concentrations as low as 0.05 mM. While the mechanism responsible for the elevation in enzyme activity is unknown, the regulation of polyamine metabolism appears to be altered in this premalignant tissue. The growth inhibition of Barrett''s epithelium-derived cell lines by ODC inhibitors suggests a potential role for these compounds in the treatment of this disease.