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Articles

Dietary Copper, Manganese and Iron Affect the Formation of Aberrant Crypts in Colon of Rats Administered 3,2'-Dimethyl-4-Aminobiphenyl^{1, ,2}

Cindy D. Davis^*,3 and Yi Feng

^* United States Department of Agriculture, Grand Forks Human Nutrition Research Center and Department of Surgery, University of North Dakota, Grand Forks, North Dakota 58202-9034.

³To whom correspondence should be addressed.

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 interactive effects of dietary copper, manganese, and iron on 3,2'-dimethyl-4-aminobiphenyl (DMABP)-induced ACF and superoxide dismutase activities in weanling rats fed low or adequate copper (0.8 or 5.1 µg Cu/g diet), low or adequate manganese (0.6 or 17 µg Mn/g diet), and adequate or high iron (37 or 140 µg Fe/g diet). Twelve rats were allowed free access to each of these eight diets for 3.5 wk prior to DMABP administration and for an additional 8 wk after the first DMABP injection. Rats fed low dietary copper had 105% (P < 0.0001) higher formation of DMABP-induced ACF than those fed adequate dietary copper. Rats ingesting low rather than adequate dietary manganese had 23% higher formation of ACF, and rats ingesting high rather than adequate dietary iron had 18% higher formation of ACF. Heart total superoxide dismutase activity was significantly correlated with the number of ACF (r = -0.43, P < 0.0001) in rats administered DMABP. These results suggest that dietary alterations that affect superoxide dismutase activity may affect cancer susceptibility.

KEY WORDS: • copper • manganese • iron • aberrant crypt foci • superoxide dismutase • rats

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