ABSTRACT
Recent studies have identified a role for the oxidation product of linoleic acid, 13-hydroxyoctadecadienoic acid (13-HODE) in cell proliferation. The enzyme 13-HODE dehydrogenase catalyzes the conversion of 13-HODE to 13-oxooctadecadienoic acid. This enzyme has been shown to correlate with the degree of differentiation of intestinal cells in both in vitro and in vivo models. Higher enzyme levels are found in more differentiated cell types. The present study was done to determine if enzyme levels of 13-HODE dehydrogenase are predictive of the differentiation status of biopsies from human colonic mucosa. Twenty-eight patients who underwent diagnostic colonoscopy (10 patients with adenocarcinoma and 18 with adenomatous polyps) had biopsies taken from both normal rectal mucosa and neoplastic mucosa. The determination of 13-HODE dehydrogenase activity was conducted by high-performance liquid chromatography analysis of all biopsy samples. Sixteen of the 18 patients with polyps had lower 13-HODE dehydrogenase activity in the adenoma than in the uninvolved rectal mucosa (P = 0.001). The colon adenocarcinomas also had less 13-HODE dehydrogenase activity in the cancer biopsy tissue than in uninvolved rectal mucosa (P = 0.041) These data are consistent with a role for 13-HODE dehydrogenase in intestinal cell differentiation. Understanding the precise role of this enzymatic reaction could be important potentially in the therapy and biology of colon cancer. In addition, measurements of 13-HODE dehydrogenase may be a useful parameter by which to ascertain the differentiation status of intestinal cells in vitro.
