Energy Metabolism of Rat Colonocytes Changes during the Tumorigenic Process and Is Dependent on Diet and Carcinogen

Manuscript received 12 December 1997. Initial reviews completed 22 January 1998. Revision accepted 27 March 1998.

Faculty of Nutrition, Texas A&M University, College Station, TX 77843-2471

Alterations in ATP production, intracellular energy levels and mitochondrial function have been shown to trigger cytokinetic events in vitro, including inhibition of cell division, abnormal or blocked differentiation and inhibition of apoptosis. Changes in colonic cytokinetics are directly related to colon tumorigenesis but alterations in energy metabolism during the tumorigenic process have never been reported. We conducted a 2 × 2 × 3 factorial design study in 120 male Sprague-Dawley rats with two diets (pectin or cellulose-supplemented), two injected subgroups (with or without the carcinogen azoxymethane, AOM) and three termination time points (6, 16 and 36 wk post-second injection). Colonocytes were isolated and incubated with their primary energy substrates (radiolabeled butyrate, glucose, glutamine and -hydroxybutyrate) for 60 min. Production of lactate, ketone bodies and CO₂ were determined. At 6 wk, there were no significant differences in metabolism among treatments. In contrast, at 16 wk, AOM-injected rats had dramatically lower rates of CO₂ production (P < 0.001) from both glucose and butyrate and lower rates of lactate and ketone body production than their saline counterparts. At 36 wk, when tumors developed, the depressed production of lactate and ketone bodies seen in AOM-injected rats at 16 wk returned to control values. However, in AOM-injected rats, CO₂ production from glucose and butyrate remained depressed. Cellulose feeding resulted in decreased oxidation of glucose, butyrate and glutamine and an increased production of ketone bodies from butyrate by colonocytes compared with pectin feeding at 36 wk. We conclude that colonocyte energy metabolism differs in AOM-injected rats vs. saline controls and changes during tumorigenesis, and suggest a relationship between intracellular energy status and changes in cell kinetics. This is the first report that such a relationship may exist in vivo.

The Journal of Nutrition Vol. 128 No. 8 August 1998, pp. 1262-1269
Copyright ©1998 by the American Society for Nutritional Sciences

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