Comparison of the reactivity of B-DNA and Z-DNA with two isosteric chemical carcinogens: 2-N,N-acetoxyacetylaminofluorene and 3-N,N-acetoxyacetylamino-4,6-dimethyldipyrido-[1,2-a:3',2' -d] imidazole.
The reactivity of nucleic acids in various conformations and two isosteric chemical carcinogens 2-N,N-acetoxyacetylaminofluorene (N-AcO-AAF) and 3-N,N-acetoxyacetylamino-4,6-dimethyldipyrido [1,2-a:3',2'-d] imidazole (N-AcO-AGlu-P-3) have been studied. Both carcinogens bind covalently to poly(dG-dC).poly(dG-dC) (B form) and to poly(dG-br5C).poly(dG-br5dC) (Z form). They also bind covalently to (dC-dG)16 and to (dG-dT)15 sequences inserted in plasmids when the inserts are in the B form but they do not bind to the inserts in the Z form. The reactivity of guanine residues at the B-Z junctions depends upon the superhelical density of the plasmids and upon the base sequences at the junction. The distribution of AGlu-P-3 modified guanines in a restriction fragment of pBR322 is not uniform and is different from that of AAF-modified guanines. The conclusion is that N-AcO-Glu-P-3 as N-AcO-AAF can probe at the nucleotide level the polymorphism of DNA. On the other hand, the non-reactivity of both chemical carcinogens and Z-DNA and the hyperreactivity of some junctions might have some importance in the understanding of chemical carcinogenesis.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives; D000099:Acetoxyacetylaminofluorene; D002273:Carcinogens; D004247:DNA; D007093:Imidazoles; D007700:Kinetics; D009690:Nucleic Acid Conformation; D011089:Polydeoxyribonucleotides; D013329:Structure-Activity Relationship
D002273:Carcinogens; D007093:Imidazoles; D011089:Polydeoxyribonucleotides; D000099:Acetoxyacetylaminofluorene; D004247:DNA; C043663:3-(N-acetoxy-N-acetylamino)-4,6-dimethyldipyrido(1,2-a-3',2'-d)imidazole; D015073:2-Acetylaminofluorene