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Articles

Dietary Selenium and Arsenic Affect DNA Methylation

Department of Biochemistry and Molecular Biology University of Arkansas for Medical Sciences Little Rock, AR 72205

	INTRODUCTION

TOP INTRODUCTION REFERENCES

 
Dear Editor:

In the December 2000 issue, Davis et al. (1) reported that the level and chemical form of selenium affect liver and colon DNA methylation in rats but that dietary arsenic does not. This study showed that dietary selenium in vivo affects DNA methylation, important in carcinogenesis (2) , and homocysteine, important in vascular disease (3 ,4) . Further, these changes in DNA methylation occurred without changes in some other key components of methyl metabolism, liver S-adenosylmethionine and S-adenosylhomocysteine. Thus this study provides some valuable in vivo data on nutritional roles of selenium and on methyl metabolism in general.

Concomitant¹ experiments in rats fed dietary arsenic for 6wk did not show significant differences in DNA methylation in vivo when arsenic-fed groups were compared with their respective arsenic-free groups. These are also important experiments because few data exist on the effects of dietary arsenic on DNA methylation in vivo (5) . This is the case despite the nearly ubiquitous presence of arsenic in food and water and considerable debate over arsenic toxicity (5 ,6) and its possible role as an ultratrace element in nutrition (7 ,8) .

Additional statistical analysis of the data of Davis et al. (1) suggests, however, that arsenic does cause hypomethylation of liver DNA in vivo. In Figure 3 of Davis et al. (1) , liver DNA methylation is compared in five groups with and without arsenic. If these data are analyzed as a whole, it is apparent that the degree of methyl acceptance in DNA is greater (rather than less) for each of the five groups given arsenic. When there are only two equally likely outcomes, the probability of obtaining one outcome is 0.5 (i.e., P = 0.5). This is analogous to a single coin flip in which the probability of one outcome (e.g., heads) is 0.5 (i.e., P = 0.5). In each comparison of DNA methyl acceptance between the groups fed 0 and 5 mg/kg diet arsenite, the probability of one 5 mg/kg group having more methyl acceptance than the respective 0 mg/kg group is 0.5 (i.e., P = 0.5). The probability of five out of five measures having this same outcome is P = (0.5)⁵ = 0.03125 (i.e., P < 0.04).¹ Thus, these arsenic-fed rats showed consistently and significantly greater liver DNA methyl acceptance when the data of Figure 3 are analyzed as a whole.

This is one statistical test by which it could be concluded that dietary arsenic causes significant hypomethylation of liver DNA in vivo (and thus greater methyl acceptance in vitro). Additional data or additional statistical analysis of the existing data may corroborate this view. A role for dietary arsenic in hypomethylation of DNA in vivo is important for understanding human health effects and for determining safe exposure limits for arsenic.

	FOOTNOTES

 
¹ It is assumed that the coin will not land on its edge. Similarly, it is reasonable to assume that the probability is very low for obtaining precisely the same values for methyl acceptance when two groups are compared. This analysis still works if there is a finite probability of precisely identical values between groups or of coins landing on their edges. If P = 0.10 for the same value occurring, or for the coin landing on its edge, then one outcome (e.g. greater methyl acceptance or heads) occurring five consecutive times has the probability (0.45)⁵ = 0.0185 (i.e. P < 0.02).

	REFERENCES

TOP INTRODUCTION REFERENCES

 

1. Davis C. D., Uthus E. O., Finley J. W. Dietary selenium and arsenic affect DNA methylation in vitro in Caco-2 cells and in vivo in rat liver and colon. J. Nutr. 2000;130:2903-2909[Abstract/Free Full Text]

2. Pogribny I. P., Basnakian A. G., Miller B. J., Lopatina N. G., Poirier L. A., James S. J. Breaks in genomic DNA and within the p53 gene are associated with hypomethylation in livers of folate/methyl-deficient rats. Cancer Res 1995;55:1894-1901[Abstract/Free Full Text]

3. Tsai J. C., Perrella M. A., Yoshizumi M., Hsieh C. M., Haber E., Schlegel R., Lee M. E. Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc. Natl. Acad. Sci. U.S.A. 1994;91:6369-6373[Abstract/Free Full Text]

4. Southern F. N., Cruz N., Fink L. M., Cooney C. A., Barone G. W., Eidt J. F., Moursi M. M. Hyperhomocysteinemia increases intimal hyperplasia in a rat carotid endarterectomy model. J. Vasc. Surg. 1998;28:909-918[Medline]

5. Abernathy C. O., Liu Y. P., Longfellow D., Aposhian H. V., Beck B., Fowler B., Goyer R., Menzer R., Rossman T., Thompson C., Waalkes M. Arsenic: health effects, mechanisms of actions, and research issues. Environ. Health Perspect. 1999;107:593-597[Medline]

6. Tchounwou P. B., Wilson B., Ishaque A. Important considerations in the development of public health advisories for arsenic and arsenic-containing compounds in drinking water. Rev. Environ. Health 1999;14:211-229[Medline]

7. Uthus E. O., Seaborn C. D. Deliberations and evaluations of the approaches, endpoints and paradigms for dietary recommendations of the other trace elements. J. Nutr. 1996;126:2452S-2459S

8. Nielsen F. H. How should dietary guidance be given for mineral elements with beneficial actions or suspected of being essential?. J. Nutr. 1996;126:2377S-2385S

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