Submitted to: Biological Trace Element Research
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/5/2008
Publication Date: 12/28/2008
Publication URL: http://handle.nal.usda.gov/10113/37278
Citation: Uthus, E.O., Ross, S. 2008. Dietary selenium (Se) and copper (Cu) interact to affect homocysteine metabolism in rats. Biological Trace Element Research. Available: http://www.springerlink.com/content/ Interpretive Summary: Previously we reported that both selenium deficiency and copper deficiency decreased plasma homocysteine (a cardiovascular risk marker) and increased plasma gluthione (an antioxidant compound) in rats. We also showed that the enzyme needed to synthesize glutathione in the liver was elevated in selenium deficiency as well as in copper deficiency. We suggested that in both deficiencies, that homocysteine (which is needed for the synthesis of glutathione) was diverted largely to the synthesis of glutathione because of the elevation of that liver enzyme. Because both selenium deficiency and copper deficiency had similar effects, we hypothesized that a combined deficiency would exacerbate the decrease in homocysteine and the increase in glutathione. In an experiment using rats we showed the at a combined deficiency of both selenium and copper does indeed result in lower homocysteine and elevated gluththione. This may have implications in oxidative defense as both selenium and copper, through antioxidant enzymes, play major roles in defense against oxidative damage.
Technical Abstract: Our previous studies have shown that selenium (Se) is protective against dimethylhydrazine (DMH)-induced preneoplastic colon cancer lesions, and protection against DNA damage has been hypothesized to be one mechanism for the anticancer effect of Se. The present study was designed to determine whether dietary selenite affects somatic mutation frequency in vivo. We used the Big Blue transgenic model to evaluate the in vivo mutation frequency of the cII gene in rats fed either a Se-deficient (0 µg Se/g diet) or Se-supplemented diet (0.2 or 2 µg Se/g diet) (n=3 rats/diet in experiment 1 and n=5 rats/group in experiment 2) and injected with DMH (25 mg/kg body weight, i.p.). There were no significant differences in body weight between the Se-deficient and Se-supplemented (0.2 or 2 µg Se/g diet) rats, but the activities of liver glutathione peroxidase (GPx) and thioredoxin reductase (TR) and concentration of liver Se were significantly lower (p<0.0001) in Se-deficient rats compared to rats supplemented with Se. We found no effect of dietary Se on liver 8-hydroxy-2’-deoxyguanosine. Gene mutation frequency was significantly lower in liver (p<0.001) than that of colon regardless of dietary Se. However, there were no differences in gene mutation frequency in DNA from colon mucosa or liver from rats fed the Se-deficient diet compared to those fed the Se-supplemented (0.2 or 2 µg Se/g diet) diet. Although gene mutations have been implicated in the etiology of cancer, our data suggest that decreasing gene mutation is not likely a key mechanism through which dietary selenite exerts its anticancer action against rat preneoplastic colon cancer lesions.