Long-term marginal copper intake by rats: Effects on copper enzyme activities and responses to dimethylhydrazine

Studies of marginal copper intake by rats generally use feeding periods of 6 weeks or less. Longer periods may abolish adverse effects due to adaptive mechanisms conserving copper. In the present study, rats were fed either adequate or marginal copper (8 or 2 mg copper/kg diet) for 6 months. Rats consuming the lower copper level showed none of three classical signs of copper deficiency: low body weight, cardiac hypertrophy, or anemia. In contrast, these rats had low activities for the serum copper enzymes ceruloplasmin, extracellular superoxide dismutase, and diamine oxidase, as well as for liver and colon superoxide dismutase 1 and heart cytochrome c oxidase. No dietary copper effects were seen for colon carcinogenesis response to treatment with dimethylhydrazine [(DMH), 30 mg/kg, intraperitoneally (i.p.), 12 weekly injections, beginning at week 5]. Carcinogenesis was assessed as total tumor numbers, number of rats with tumors, and tumor mass per rat. For the latter, the mean value was much higher in the marginal group, but the effect was not statistically significant. DMH treatment caused anemia in the marginal but not in the adequate group. The anemia did not involve variations in ceruloplasmin activities but may have involved low diamine oxidase activities. In summary, long-term, marginally low copper intake produced low activities for a number of copper enzymes and produced an anemia response to DMH. J. Trace Elem. Exp. Med. 13:359–365, 2000. © 2000 Wiley-Liss, Inc.