Molecular Pharmacology, Vol 2, 570-573, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

Studies on Depurination and Alkylation of DNA’s of Different Base Compositions

¹ Department of Medical Microbiology and Immunology, Department of Biological Chemistry, and Molecular Biology Institute, University of California, Los Angeles, California 90024

DNA’s from four different sources, varying in G + C content from 36% to 72%, were subjected to depurination by heating at neutral pH (100°, 24 hr) or to alkylation (dimethyl sulfate, 37°); the extent of alkylation was measured by total release of 7-N-methylguanine by heating at neutral pH (100°, 4 hr). The fraction of guanine or adenine released by depurination and the fraction of guanine alkylated were found to be independent of G + C content, i.e., independent of the average base distribution or base densities along the DNA molecule. These two reactions (depurination at neutral pH and alkylation) have been implicated as causes of spontaneous and induced mutability. If, indeed, these reactions under the conditions studied are representative of the mutagenic processes in vivo, then causes other than variations in base distributions must be sought to explain the fact that observable mutabilities vary along the molecule of DNA.

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ACKNOWLEDGMENT This investigation was supported by grants CA-08128 and HD-01331 from the National Institutes of Health, U. S. Public Health Service, and E-52 from the American Cancer Society.