Effect of dietary copper on colonic tumor production and aortic integrity in the rat

Gastrointestinal malignancy has been associated with aortic aneurysmal disease in humans, while metabolic derangement of copper has been incriminated as a possible promotor of aneurysmal development of the aorta. An animal model utilizing the carcinogen 1,2-dimethylhydrazine (DMH) was selected to evaluate levels of dietary copper on both colonic tumor production and morphologic changes in the rat aorta. Six groups, each including 10 Sprague-Dawley rats, received 16 weekly doses (20 mg/kg) of DMH beginning at 4 weeks of age. Groups were maintained on either normal (25 ppm), low (0.6 ppm), or high (100 ppm) copper chow during the entire experimental period. After 25 weeks, all animals were sacrificed to assess colonic tumor production and to perform scanning (SEM) and transmission electron microscopic (TEM) studies of the rat aorta. Results showed a significant increase in colonic tumor production (3.14 +/- 0.39 tumors per centimeter colon) in rats treated with low-copper chow and DMH when compared with rats on normal chow and DMH (0.74 +/- 0.07 tumors per centimeter colon) and animals maintained on high-copper diets and DMH (0.76 +/- 0.08 tumors per centimeter colon). In addition, morphologic study showed disruption of the intima and media in rats maintained on low-copper diet alone, and also on low-copper diet plus DMH. The results of this study showed that DMH and low dietary copper significantly increase (P less than 0.001) the yield of colonic tumors and produce loss of aortic integrity when studied morphologically. Copper levels may be important in the association of neoplasia and aneurysm formation in the clinical setting.