Enzymatic methylation of DNA and poly(dG-dC) X poly(dG-dC) modified by 4-acetoxyaminoquinoline-1-oxide, the ultimate carcinogen of 4-nitroquinoline-1-oxide.
Both the initial velocity and the overall methylation of Ac-4HAQO modified DNA by a calf brain DNA (cytosine-5-)-methyltransferase are increased as compared to native DNA. The affinity of the modified DNA for the enzyme decreases as a function of the extent of the modification. Heat-denatured, single-stranded DNA shows exactly the opposite results: the more it is modified, the less it is methylated. The poly(dG-dC) X poly(dG-dC) modified by 4NQO is as well methylated as the non-modified one. The carcinogen may induce a tertiary structure favouring the 'walking' of the enzyme along the DNA. The hypermethylation caused by this carcinogen could have a significance in gene activity and cellular differentiation.
D000634:Aminoquinolines / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002273:Carcinogens / Q000378:metabolism*; D002417:Cattle; D002645:Chickens; D004247:DNA / Q000097:blood / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D007700:Kinetics; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D011089:Polydeoxyribonucleotides / Q000378:metabolism*; D013379:Substrate Specificity
D000634:Aminoquinolines; D002273:Carcinogens; D011089:Polydeoxyribonucleotides; C019530:poly(dC-dG); C032982:4-acetoxyaminoquinoline 1-oxide; D004247:DNA; D008780:Methyltransferases; D004248:DNA (Cytosine-5-)-Methyltransferases