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Rat Colonic Antioxidant Status: Interaction of Dietary Fats with 1,2-Dimethylhydrazine Challenge^1,2,

Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430

The polyunsaturated fatty acid composition of dietary fat has been associated with increased oxidant stress in tissues. We previously showed that antioxidant mechanisms in colon mucosa are affected by dietary fat. In this study, the colonic antioxidant response to treatment with the colon-specific carcinogen 1,2-dimethylhydrazine (DMH) was determined. Sprague-Dawley rats were fed one of four AIN-76A-based diets with varied fat content. The basal diet contained 5% corn oil, the menhaden oil diet contained 19% menhaden oil and 1% corn oil, the corn oil diet contained 20% corn oil and the beef tallow diet contained 19% beef tallow and 1% corn oil. Animals were given one or two intraperitoneal injections of either DMH (20 mg/kg) or 1 mmol/L EDTA. Homogenates of colon mucosa were assayed to determine activity of catalase, glutathione peroxidase, total superoxide dismutase, manganese superoxide dismutase, glutathione reductase and glutathione-S-transferase, as well as total glutathione concentration, thiobarbituric acid-reacting substances and nuclear aberrations. Total glutathione concentration was greater in rats fed all diets following two injections of DMH, whereas glutathione reductase activity remained unchanged relative to controls. Lipid peroxidation was highest in the group fed menhaden oil; nuclear aberrations were greatest in the corn oil-fed group. In conclusion, both type and amount of dietary fat modified the response of colon tissue to genotoxic challenge, but none of the diets seemed more protective than the others.

KEY WORDS: • fat • 1,2-dimethylhydrazine • rats • antioxidant enzymes • lipid peroxidation

¹ Supported in part by the Beef Industry Council of the National Live Stock and Meat Board and by the Institute for Nutritional Sciences of Texas Tech University and Health Sciences Center.

² Presented in part at the 74th Annual Meeting of the Federation of American Societies for Experimental Biology, April 1990, Washington, DC. [Kuratko, C. N. & Pence, B. C. Effect of different dietary fats and 1,2-dimethylhydrazine on oxygen radical detoxification in rat colon. FASEB J. 4: 666 (abs.)].

Manuscript received 24 September 1990. Revision accepted 18 July 1991.