Dietary lipotrope-mediated carcinogenesis in female rats
1998
Moon, Y.S. | Keller, W.L. | Park, C.S.
Dietary deficiency of lipotropes is known to be carcinogenic in itself. This study examined 1) the susceptibility of female rats previously exposed to lipotrope-modified diets to nitrosomethylurea (NMU)-induced mammary carcinogenesis; and 2) how lipotrope-modified diets modulate DNA methylation and gene expression in mammary tissue. Female rats (36 d of age) were assigned to one of the following groups: control-synthetic diet (CSD), containing all required lipotropes; methyl-deficient diet (MDD), lacking all lipotropes; and methyl-additive diet (MAD), containing 1.5-fold the amount of each lipotrope as in CSD. Rats were injected with NMU after a 2-wk dietary treatment period, and 2 d after NMU administration all treatment groups were fed CSD for the remaining experimental period. Mammary tissues were collected from rats just prior to NMU administration. The MDD group had the shortest latency period. The number of tumors and tumor volume were greatest in the MDD rats. Dietary modification of lipotropes altered the DNA methylation pattern of ornithine decarboxylase gene. DNA was significantly hypomethylated in mammary tissues of the MDD rats. These results suggest that dietary deficiency of lipotropes led to changes in DNA methylation and enhanced NMU-induced mammary carcinogenesis.
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