An ultimate chemical carcinogen, N-acetoxy-2-acetylaminofluorene, detects non-B DNA structures that are reactive with chloroacetaldehyde in supercoiled plasmid DNA.
A model ultimate carcinogen, N-acetoxy-2-acetylaminofluorene (N-acetoxy-AAF), reacts with specific DNA sites in supercoiled plasmid DNA that assume non-B DNA structures. The reaction was studied using supercoiled plasmid DNA harboring either inverted repeats or poly(dG)--poly(dC) sequences, the sequences which are known to adopt non-B DNA structure when under torsional stress. The sites of modification were determined by first digesting the chemically treated DNA with a restriction enzyme, and then by digesting the site of modification with S1 nuclease. Southern blot analysis of resulting DNA fragments revealed that N-acetoxy-AAF detects non-B DNA structures in common with another chemical carcinogen, chloroacetaldehyde, which reacts specifically with unpaired adenine and cytosine residues. These results suggest that specific DNA sites with unpaired DNA bases in supercoiled plasmid DNA, and possibly similar structures in chromatin, are hot-spots for certain chemical carcinogen attack.
Kohwi-Shigematsu
T
T
Cancer Research Center, La Jolla Cancer Research Foundation, CA 92037.
Scribner
N
N
Kohwi
Y
Y
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism; D000099:Acetoxyacetylaminofluorene / Q000378:metabolism*; D001483:Base Sequence; D004278:DNA, Superhelical / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D009690:Nucleic Acid Conformation; D010957:Plasmids
D004278:DNA, Superhelical; D000099:Acetoxyacetylaminofluorene; D015073:2-Acetylaminofluorene; C004656:chloroacetaldehyde; D000079:Acetaldehyde; D008274:Magnesium