SOURCES OF VARIABILITY IN ESTIMATING ORNITHINE DECARBOXYLASE ACTIVITY AND POLYAMINE CONTENTS IN HUMAN COLORECTAL MUCOSA

The activity of ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, is elevated during epithelial carcinogenesis. Since this enzyme is a target for colon and other cancer chemoprevention strategies, we sought to identify sources of variability affecting the measurement of tissue ODC activities and polyamine contents. Multiple colorectal biopsies were obtained from 39 patients undergoing colonoscopy. Biopsy size affected polyamine but not ODC values. Spermidine (spd):spermine (spm) ratios varied less than the contents of the individual amines. Bowel preparation methods did not affect any of the measurements. ODC activities and spd:spm ratios did not vary with bowel location. Lab assay methods contributed to sources of error. Variability was greatest for polyamine content measurements but was reduced when polyamine contents were analyzed as spd:spm ratios. intrapatient variability of these parameters was as great or greater than interpatient variability. When measured in apparently unaffected colorectal mucosa, none of these parameters were significantly correlated with prior polyp history, number of prevalent polyps found at current colonoscopy, or polyp size. Thus, neither ODC activity nor polyamine contents of normal mucosa appear to be discriminatory markers of colorectal carcinogenesis. However, spd:spm ratios, which show the least variability among measures of polyamine contents, should be a good marker of the consequence of polyamine synthesis inhibition in chemoprevention trials.