Acridine mutagens and DNA structure

Abstract

A number of independent critical structural parameters, which have been determined by studies on sedimentation, low angle X-ray scattering, flow dichroism, flow-polarized fluorescence, and chemical reactivity, provide the evidence for intercalation of the acridines between two otherwise sequential base pairs, and require the rejection of various alternative hypotheses. The binding requires a local untwisting and extension of the double helix, which is found to be compatible with the normal structural and bonding parameters. The expectation of a substantial alteration in the chemical reactivity of intercalated molecules because of their inaccessibility to electrophilic attack has been verified by reaction rate studies. Study of the relation between viscosity enhancement in dilute DNA solutions and intercalation has been extended using very low shear viscometry. The results agree with the earlier measurements in that the enhancement is observed with the binding of intercalatable cations, while others yield a slight diminution. A pronounced stabilization of the double helix is found, corresponding to a substantially raised thermal transition temperature. Intercalation into polyribonucleotide complexes formed between poly A and poly U renders the double helix substantially more stable than the triple. While intercalation seems to be prerequisite for mutagenicity of the insertion-deletion type, the acridine structure is not essential, nor are all intercalating molecules mutagenic.