ELEVATED EXPRESSION AND ALTERED PATTERN OF ACTIVITY OF DNA METHYLTRANSFERASE IN LIVER-TUMORS OF RATS FED METHYL-DEFICIENT DIETS

DNA methyltransferase (MTase) activity in nuclear extracts from neopla stic and preneoplastic livers of rats fed a methyl-deficient diet (MDD ) is elevated compared with that seen in the livers of control rats. N uclear proteins were prepared in the presence of protease inhibitors i ncluding trans-epoxy succinyl-L-leucylamido-(4-guanido)butane and were fractionated by isoelectric focusing. In normal, control liver, two d istinct MTase fractions were observed. In MDD-induced malignant liver, a third fraction, in addition to the previous two, was also seen. Bot h the DNA substrate and the cytosine site specificities of the third M Tase fraction differ from those of the other two fractions. The distin ct MTase activity in liver tumor has significantly more de novo MTase activity than do the MTase fractions of normal, control liver. Thus, n ormal and neoplastic rat livers differ in DNA MTase fractionation patt erns and site specificities, The altered DNA MTase activity observed i n rat liver tumors caused by MDDs may be one of the critical factors c ontributing to cancer formation through abnormal DNA methylation.