Molecular Pharmacology, Vol 6, 315-322, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Interaction of 4-Nitroquinoline 1-Oxide with Deoxyribonucleic Acid and Synthetic Polydeoxyribonucleotides

¹ University of Texas Southwestern Medical School, Department of Pathology, Dallas, Texas 75235, and Laboratories for Cell Research, Woodlawn Hospital, Dallas, Texas 75219

Native calf thymus DNA and, to a lesser extent, poly dG:dC produced marked changes in the absorption spectrum of 4-nitroquinoline 1-oxide (4-NQO) as determined by difference spectrum measurements. Poly d(A-T) or denatured calf thymus DNA caused minor changes in the absorption spectrum of 4-NQO, using difference spectrum methods.

The addition of sodium chloride from 0.5 mM to 1.0 M decreased the effect of native DNA on the difference spectrum of 4-NQO by approximately 4-fold. The interaction was partially dependent upon ionic parameters, which suggested the importance of charged sites in the interaction of 4-NQO with DNA.

Urea (6 M) abolished the effect of DNA on the difference spectrum of 4-NQO. The effect of urea may indicate some role of hydrogen bonding in the formation of the DNA-4-NQO complex or in the alteration of hydrophobic interactions resulting in disruption of the DNA-4-NQO complex.

Strand separation (T_m) of native DNA was significantly stabilized by the addition of 4-NQO.

Studies on the binding of native DNA with 4-NQO resulted in a nonlinear curve, consistent with the involvement of more than one site of interaction in the formation of the DNA-4-NQO complex.

The integrity of the double-helical conformation of DNA and the presence of G-C pairs appeared to be essential for maximal complex formation. The binding of 4-NQO to DNA evidently is complex and cannot be described by a single model of complex formation.