Mutagenic and Inactivating DNA Alterations

Abstract

typic consequences has greatly benefited from the advancement of biochemical and genetic methods. 1. The alteration of nucleic acid bases can be measured by UV,1 infrared and nuclear magnetic spectra, use of radioactive bases in nucleic acids, chromatography, and straightforward chemistry. Cross-linking can be shown by reversible DNA denaturation, and backbone breakage by decreases in the sedimentation constant, viscosity, or light scattering. To uncover the primary site of attack and the high specificity of some chemicals toward nucleic acids, synthetic oligo- and polynucleotides will have to be increasingly used. 2. The methods for determining the phenotypic consequences of nucleic acid alterations range far afield. Chromosomal breaks and large chromosomal alterations can be determined cytologically or by classical genetic methods. The extent and specificity of small nucleic acid alterations can be analyzed both by genetic fine structure measurements and by the specificity of forward and reverse mutation induction. The correlation between nucleic acid alterations and genetic investigations has been possible mainly by the use of viruses or transforming DNA for which the effect of chemicals can be safely attributed to the direct effect on nucleic acids. Finally, the analysis of mutagenic nucleic acid alterations can be used, together with in vitro experiments on protein synthesis, to determine the base sequence of some genetic regions. The consistency of these results checks in turn the validity of the genetic and biochemical conclusions.