DIETARY LIPOTROPE-MEDIATED MAMMARY CARCINOGENESIS IN FEMALE RATS

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-synth etic diet (CSD), containing all required lipotropes; methyl-deficient diet (MDD), lacking all lipotropes; and methyl-additive diet (MAD), co ntaining 1.5-fold the amount of each lipotrope as in CSD. Rats were in jected 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 pr ior to NMU administration. The MDD group had the shortest latency peri od. The number of tumors and tumor volume were greatest in the MDD rat s. Dietary modification of lipotropes altered the DNA methylation patt ern of ornithine decarboxylase gene. DNA was significantly hypomethyla ted in mammary tissues of the MDD rats. These results suggest that die tary deficiency of lipotropes led to changes in DNA methylation and en hanced Nh NMU-induced mammary carcinogenesis. (C) 1998 Elsevier Scienc e Inc.