Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/17/1999
Publication Date: N/A
Interpretive Summary: Colon cancer is the second leading cause of cancer deaths in the United States and the fourth most common cause of cancer deaths worldwide. Anatomical lesions leading to cancer have been detected in human colons and in experimental animals treated with chemicals that cause cancer. Altered levels of antioxidant enzymes, known as superoxide dismutases, have been implicated in cancer development in both humans and experimental animals. Dietary factors are potential modulators of superoxide dismutase activity. The current study investigated the effects of dietary copper, manganese and iron on anatomical lesions and superoxide dismutase activities in animals treated with a chemical that causes cancer. We observed that the frequency of these anatomical changes was significantly increased in animals fed low dietary copper and tended to be increased in animals fed low dietary manganese and high dietary iron. Changes in the frequency of these anatomical lesions correlated with changes in superoxide dismutase activity; this suggests that dietary alterations affecting superoxide dismutase activity may affect cancer susceptibility. These results have practical implications because diets in the United States are often low in copper.
Technical Abstract: Aberrant crypt foci (ACF) are preneoplastic lesions for colon cancer. Altered amounts of copper-zinc (CuZnSOD) and manganese (MnSOD) superoxide dismutases have been implicated in multistage carcinogesis of both rodents and humans. Dietary factors are potential modulators of both CuZnSOD and MnSOD activity. The purpose of this study was to investigate the inter- active effects of dietary copper, manganese and iron on 3,2 dimethyl- 4-aminobiphenyl (DMABP)- induced ACF and superoxide dismutase activities in weanling rats fed two concentrations of copper (0.8 or 5.1 ug Cu/g diet), two concentrations of manganese (0.6 or 17 ug Mn/g diet) and two concentrations of iron (37 or 140 ug Fe/g diet). Compared to adequate dietary copper, ingestion of low dietary copper increased the formation of DMABP-induced ACF by 015% (p<0.0001). Ingestion of low dietary manganese caused increase in the formation of ACF and ingestion of high dietary iron caused an 18% increase in the formation of ACF; howeover, these difference were not statistically significant. The highest heart total superoxide dismutase activity was observed in the animals fed adequate dietary copper and manganese and the lowest heart superoxide dismutase activity was observed in the animals fed low dietary copper and manganese. These results suggest that dietary alterations which affect superoxide dismutase activity may affect cancer susceptibility.