Dietary arsenic affects dimethylhydrazine-induced aberrant crypt formation and hepatic global DNA methylation and DNA methyltransferase activity in rats |
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Authors: | Eric O Uthus Cindy Davis |
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Institution: | (1) ARS, Grand Forks Human Nutrition Research Center, United States Department of Agriculture, 58202 Grand Forks, ND;(2) Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, NIH, DHHS, 20892 Rockville, MD |
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Abstract: | Cell culture studies have suggested that arsenic exposure results in decreased S-adenosylmethionine (SAM), causing DNA hypomethylation. Previously, we have shown that hepatic SAM is decreased and/or S-adenosylhomocysteine increased in arsenic-deprived rats; these rats tended to have hypomethylated DNA. To determine, the
effect of dietary arsenic on dimethylhydrazine (DMH)-induced aberrant crypt formation in the colon, Fisher 344 weanling male
rats were fed diets containing 0,05, or 50 μg As (as NaAsO2)/g. After 12 wk, dietary arsenic affected the number of aberrant crypts (p<0.02) and aberrant crypt foci (p<0.007) in the colon and the amount of global DNA methylation (p<0.04) and activity of DNA methyltransferase (DNMT) (p<0.003) in the liver. In each case, there were more aberrant crypts and aberrant crypt foci, a relative DNA hypomethylation,
and increased activity of DNMT in the rats fed 50 μg As/g compared to those fed 0.5 μg As/g. The same phenomenon, an increased
number of aberrant crypts and aberrant crypt foci, DNA hypomethylation, and increased DNMT tended to hold when comparing rats
fed the diet containing no supplemental arsenic compared to rats fed 0.5 μg As/g. The data suggest that there is a threshold
for As toxicity and that possibly too little dietary As could also be detrimental.
The U.S. Department of Agriculture, Agricultural Research Service. Northern Plains Area is an equal opportunity/affirmative
action employer and all agency services are available without discrimination. |
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Keywords: | Arsenic cancer animal model dimethylhydrazine aberrant crypt methylation |
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