Synthesis of colonic membrane phospholipids is altered during tumorigenesis and is affected by diet.
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Phospholipid composition and mass of cell membranes are known to change during the tumorigenic process. However, the effect of diet and carcinogen on colonie mucosa phospholipids has not been reported. We conducted a 2 2 2 factorial design study using 80 male Sprague Dawley rats (2 fibers, pectin and cellulose; + or - the carcinogen azoxymethanc, AOM; at 2 time points, 16 and 36 wk post AOM injection). Isolated colonocytes were incubated with 'C-labeled glucose, butyrate, arachidonate or linoleate for 60 min. Cells were harvested, lipids extracted, and lipid classes were separated by thin-layer chromatography. Incorporation of radiolabeted substrates into specific lipid classes was determined. At 16 wfc, total lipid synthesis from glucose or butyrate was lower in AOM-treated animals than in their saline-counterparti (P<0.05). In contrast, at the final time point when macroscopic adenocarcinomas were observed in 70% of the animals in both fiber groups, total lipid synthesis from glucose increased in tumor-bearing animals as compared to saline controls or AOM-animals without tumors (PO.05). Total lipid synthesis from butyrate was higher in pectin vs cellulose supplemented rats at mis time. Phospholipids accounted for 80 and 20% of total lipids svnthfsianH from glucose and butyrate, respectively. Incorporation of arachidonic acid or linoleic acid into phospholipids, including phosphatidylcholine, pbmphatidylethanolamine and phosphatidylinositol was also higher in tumor-bearing animals than in non-tumor bearing AOM-injected animals or saline controls (PO.05). These data show that diet and carcinogen alter the synthesis of mucosal phospholipids during the tumorigenic process. Supported by NIHCA 61750.