Equilibrium binding of carcinogens and antitumor antibiotics to DNA: site selectivity, cooperativity, allosterism.
The equilibrium binding of the carcinogens N-hydroxy-N-acetyl-2-amino-fluorene (HAAF) and 4-nitroquinoline-1-oxide (NQO) to phi X174RF DNA have been studied by phase partition techniques. Both molecules bind in a cooperative manner with only a few carcinogen molecules binding to each phi X174RF DNA molecule. The binding data for both HAAF and NQO fit a model in which two carcinogens cluster into a small number of sites--four sites for HAAF and twelve sites for NQO. Phase partition techniques were also used to study the binding of actinomycin D to both calf thymus DNA and poly (dG-dC) . poly (dG-dC) at much lower r values than had been previously reported. These data exhibit humped Scatchard plots which are indicative of cooperative binding; the overall shape of the Scatchard plots are consistent with a model for drug induced allosteric transitions in the DNA structure. The cooperativity in the actinomycin D binding to calf thymus DNA increases with decreasing sodium chloride concentration, suggesting a role for DNA flexibility in allosteric binding.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives; D015112:4-Nitroquinoline-1-oxide; D000818:Animals; D010584:Bacteriophage phi X 174; D001482:Base Composition; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D004279:DNA, Viral; D003609:Dactinomycin; D006881:Hydroxyacetylaminofluorene; D007700:Kinetics; D009600:Nitroquinolines; D011089:Polydeoxyribonucleotides; D013950:Thymus Gland
D004279:DNA, Viral; D009600:Nitroquinolines; D011089:Polydeoxyribonucleotides; D003609:Dactinomycin; C016681:poly(dG).poly(dC); D006881:Hydroxyacetylaminofluorene; D015112:4-Nitroquinoline-1-oxide; D004247:DNA; D015073:2-Acetylaminofluorene