QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Davis, C. D. Articles by Uthus, E. Search for Related Content PubMed Articles by Davis, C. D. Articles by Uthus, E.

---

Articles

Reply to Craig A. Cooney

Grand Forks Human Nutrition Research Center Grand Forks, ND 58203

	INTRODUCTION

TOP INTRODUCTION REFERENCES

 
Dear Editor:

We appreciate Dr. Cooney’s interest in our article and thank him for his positive comments. We agree with Dr. Cooney that determining the role for dietary arsenic on the methylation of DNA in vivo is important for understanding human health effects and for determining safe exposure limits for arsenic. In our study, arsenic tended (P < 0.08, two-way ANOVA) to cause hypomethylation of liver DNA in vivo (1) . Dr. Cooney suggests that additional statistical analysis would show a significant effect of dietary arsenic on liver DNA methylation [Fig. 3 of (1) ] based on a mathematical approach using 5 coin tosses as an example. However, comparing the means (heights of the bar graphs) ignores the variability in the data. Although graphically the means for the rats fed 5 µg/g dietary arsenic appear larger than the means for those not supplemented with dietary arsenic, there were no significant differences in any of the five selenium groups when assessed by t-tests. Thus, his analogy is not valid because it assumes that there are differences in each of the treatments between the arsenic-supplemented and nonsupplemented rats, when in fact no differences exist.

Because determining the role of dietary arsenic on methylation of DNA in vivo is important, we want to emphasize that the diets referred to by Dr. Cooney as "arsenic free" actually contain 44 ng As/g (1) . This amount of arsenic is similar to a proposed requirement for arsenic (25–50 ng/g) by Uthus (2) . Recent findings in Uthus’ laboratory showed that compared with rats fed adequate arsenic, those fed either deficient (<5 ng/g) or excess (50 µg/g) arsenic had global DNA hypomethylation in the liver. Thus, it is possible that the trend of greater methyl acceptance (indicative of hypomethylation) seen in the rats fed supplemental arsenic [Fig. 3 of (1) ] is a similar phenomenon. That is, those fed the diets supplemented with 5 µg As/g received an amount of arsenic that started to induce DNA hypomethylation. Perhaps if the rats were fed diets containing >5 µg As/g, the change would have been significant. On the other hand, it should be noted that recent findings by Uthus (unpublished observations) showed that low arsenic intake (<5 ng/g diet) also induced hypomethylation compared with rats fed 0.5 µg/g. To summarize, arsenic is thought to have a role in methionine metabolism and it has been proposed by one of us (E.O.U.) that feeding diets containing too little or too much arsenic will cause DNA hypomethylation [that is, you will see a response similar to that shown in Fig. 1 of (1) ]. Studies are ongoing at the USDA, ARS Grand Forks Human Nutrition Research Center by Dr. Uthus to ascertain the consequences of hypomethylation of DNA caused by feeding laboratory animals very low (<5 ng/g) or moderately elevated (>5 µg/g) arsenic.

	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. Uthus E.O. Estimation of safe and adequate daily intake for arsenic. Mertz W. Abernathy C. O. Olin S. S. eds. Risk Assessment of Essential Elements 1994:273-282 ISLI Press Washington, DC.

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Davis, C. D. Articles by Uthus, E. Search for Related Content PubMed Articles by Davis, C. D. Articles by Uthus, E.