Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 12/10/2000
Publication Date: 3/7/2001
Citation: Davis, C.D., Uthus, E.O. 2001. Dietary selenium and methylation status affect dimethylhydrazine-induced aberrant crypt formation in rat colon [abstract]. The Federation of American Societies for Experimental Biology Journal. 15:A952.
Technical Abstract: Several observations implicate a role for altered DNA methylation in cancer pathogenesis. We have recently observed global hypomethylation of liver and colon DNA of animals fed a selenium-deficient diet and in Caco-2 cells cultured in the absence of selenium. The purpose of this study was to investigate whether the DNA methyltransferase inhibitor, 5-aza-2'- deoxycytidine would alter the effect of dietary selenium on the formation of aberrant crypts. Sixty weanling rats were fed three concentrations of selenium in a Torula yeast based diet. Half of the animals were injected weekly with 5-aza-2'-deoxycytidine (1 ug/g, sc) and half injected with the vehicle control. After 3.5 weeks on the experimental diets, the animals were given two injections of dimethylhydrazine (25 mg/kg, i.p.). Animals fed the selenium deficient diet and injected with PBS had a significantly (p<0.006) higher number of aberrant crypts than animals fed 0.1 or 2.0 ppm selenium (244+/-21 vs 165+/-9 and 132+/-14, respectively). In contrast, when animals were injected with 5-aza-2'-deoxycytidine, there was a significant (p<0.0001) reduction in aberrant crypt formation and dietary selenium did not affect aberrant crypt formation (62+/-8 vs 77+/-13 vs 54+/-8, in animals fed 0, 0.1 and 2.0 ppm selenium, respectively). Animals fed the selenium deficient diet had significantly (p<0.0001) lower serum, erythrocyte and liver glutathione peroxidase activities; colon, plasma and liver selenium concentrations; and plasma homocysteine and cysteine concentrations. 5-Aza-2'-deoxycytidine treatment caused a significant (p<0.03) decrease in plasma homocysteine concentrations. These results suggest that decreased DNA methyltransferase activity may protect selenium deficient animals against carcinogen-induced aberrant crypt formation.