ARS | Publication request: DIETARY ARSENITE AFFECTS DIMETHYLHYDRAZINE (DMH)-INDUCED ABERRANT CRYPT FORMATION IN COLON AND GLOBAL DNA METHYLATION IN LIVER OF RATS

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: December 2, 2002
Publication Date: March 14, 2003
Citation: Uthus, E.O., Davis, C.D. 2003. Dietary arsenite affects dimethylhydrazine (DMH)-induced aberrant crypt formation in colon and global DNA methylation in liver of rats [abstract]. The Federation of American Societies for Experimental Biology Journal. 17:A1152.

Technical Abstract: Previous work has shown that arsenic (As) affects methionine metabolism. Alterations in methionine metabolism can affect cancer processes. To determine the effect of dietary As on DMH-induced aberrant crypt formation in colon Fisher-344 male, weanling rats (N=20/group) were fed diets containing 0, 0.5, or 50 µg As (as NaAsO**2)/g; the basal diet contained <10 ng As/g. DMH dosing occurred at wk 3 and 4 of the 12 wk experiment. Dietary As affected the number of aberrant crypts (p<0.02) and aberrant crypt foci (p<0.007) in colon and the amount of global DNA methylation in liver (p<0.04). In each case, there were more aberrant crypts and aberrant crypt foci and a relative DNA hypomethylation 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 and DNA hypomethylation, tended to hold when comparing rats fed the diet containing no supplemental As compared to rats fed 0.05 µg As/g. Aberrant crypts and aberrant crypt foci are preneoplastic lesions and are related to the number of tumors that ultimately develop. Also DNA hypomethylation has been associated with cancer. Thus, the data suggest that there is a lower threshold for As toxicity and that possibly too little dietary As could also be detrimental.