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Both the initial velocity and the overall methylation of DNA modified by acetylamino-4,6-dimethyldipyrido(1,2-a:3',2'-d)imidazole (A-Glu-P-3) by rat liver DNA-(cytosine-5-)-methyltransferase are decreased as compared to native DNA. A-Glu-P-3 bound to guanine residues may block the movement of the enzyme along the helix. The modified DNA does not inhibit the enzymatic methylation of native DNA. The enzyme has a lower affinity for the modified DNA than for native DNA. The hypomethylation caused by this carcinogen could have a significance in gene activity, cellular differentiation and cancer induction.
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