Chemical modification of nucleic acids by alkylating agents continues to be extensively explored from the perspective of chemical mutagenesis and carcinogenesis. Largely through the pioneering in vitro and in vivo studies of Lawley (1961), Lawley and Brookes (1963), Singer (1972), and Reese and coworkers (1965), coupled with theoretical predictions of Pullman (1974), a detailed profile has emerged of the principal alkylation sites for purine and pyrimidine nucleotides. Generally, alkylation of nucleic acids produces a multiplicity of reaction products dependent upon factors such as nature of base ring, electrophilicity of the alkylating agent (Lawley, 1976), and presence of activating enzymes (Magee and Barnes, 1967). Thus, for example, alklation of adenine nucleotides can occur at six sites, Figure 1. Strong electrophiles such as N-methyl-N-nitrosourea (MNUA) and N-methyl-N1-nitro-N-nitrosoguani-dine (MNNG) couple preferentially with available oxygen donors, e.g., phosphate group, 2′ oxygen in ribonucleotides, while weakly electrophilic agents dimethyl sulfate and methyl methane sulfonate tend to show a higher proportion of ring nitrogen methylation at N1, N3, and N7 of purines.