In vitro enzymatic methylation of DNA modified with the mutagenic amine: 3-N,N-acetoxyacetylamino-4,6-dimethyldipyrido(1,2-a:3'2'-d )imidazole.
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.
D015073:2-Acetylaminofluorene / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000494:pharmacology*; D007093:Imidazoles / Q000378:metabolism*; D007700:Kinetics; D008745:Methylation; D009153:Mutagens / Q000378:metabolism*
D007093:Imidazoles; D009153:Mutagens; D004247:DNA; C043663:3-(N-acetoxy-N-acetylamino)-4,6-dimethyldipyrido(1,2-a-3',2'-d)imidazole; D015073:2-Acetylaminofluorene; D004248:DNA (Cytosine-5-)-Methyltransferases