Author
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Uthus, Eric |
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ROSS, SHARON - NIH, NAT CANCER INSTITUTE |
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DAVIS, CINDY - NIH, NAT CANCER INSTITUTE |
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Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/20/2005 Publication Date: 3/17/2006 Citation: Uthus, E.O., Ross, S., Davis, C.D. 2006. Differential effects of dietary selenium (se) and folate on methyl metabolism in liver and colon of rats. Biological Trace Element Research. 109:201-214. Interpretive Summary: Selenium and folate, both components of foods, have been shown protective for certain forms of cancer. Animals fed diets low in folate are more prone to cancer. On the other hand, selenium is anticarcinogenic when fed or supplemented at more than the recommended intake (supranutritional). In a recent study, we showed that, in rats fed a diet deficient in selenium compared to those fed supranutritional amounts of selenium, there were differences in certain metabolic reactions ' those involving a process called methylation. However, it was unclear whether the effects of dietary treatment on methylation were the result of selenium deficiency or supplementation. Also, no previous study has undertaken to determine how adequate dietary selenium and folate interact with each other in the process of preventing cancer. Thus, an animal experiment was conduced to ascertain the effect of adequate versus deficient dietary selenium and folate on various biomarkers of cancer including methylation. Rats were fed diets either deficient or adequate in folate and deficient or adequate in selenium. The results suggested that selenium deficiency is a more important modifier of methylation than either adequate or supplemental selenium. However, the results also support the concept that when studying folate, selenium status should be monitored and, vice versa, when studying selenium, folate status should be monitored. Understanding this interaction between selenium and folate may help determine the mechanism of cancer protection afforded by folate and high dietary (supranutritional) selenium. Technical Abstract: A previous study compared the effects of folate on methyl metabolism in colon and liver of rats fed a selenium-deficient diet (<3 µg Se/kg) to those of rats fed a diet containing supranutritional Se (2 mg selenite/kg). The purpose of this study was to investigate the effects of folate and adequate Se (0.2 mg/kg) on methyl metabolism in colon and liver. Weanling, Fischer-344 rats (n=8/diet) were fed diets containing 0 or 0.2 mg selenium (as selenite)/kg and 0 or 2 mg folic acid/kg in a 2 x 2 design. After 70 d, plasma homocysteine was increased (p<0.0001) by folate deficiency; this increase was markedly exacerbated (p<0.0001) in rats fed 0.2 mg Se/kg compared to the selenium-deficient diet. The activity of hepatic glycine N-methyltransferase (GNMT) was increased by folate deficiency (P<0.006) and decreased by selenium deprivation. Colon and liver S-adenosylhomocysteine were highest (p<0.006) in rats fed deficient folate and adequate selenium. Although folate deficiency decreased liver S-adenosylmethionine (SAM, p<0.0001), it had no effect on colon SAM. Global DNA methylation was decreased (p<0.04) by selenium deficiency in colon but not liver; folate had no effect. Selenium deficiency did not affect DNA methyltransferase (Dnmt) activity in liver but tended to decrease (p<0.06) the activity of the enzyme in the colon. Dietary folate did not affect liver or colon Dnmt. These results in rats fed adequate selenium are similar to previous results found in rats fed supranutritional selenium. This suggests that selenium deficiency appears to be a more important modifier of methyl metabolism than either adequate or supplemental selenium. Additionally, we showed for the first time that dietary selenium increases the activity of liver glycine N-methyltransferase, an enzyme involved in the regulation of tissue SAM and SAH. |
