“Excision” of Bases from DNA Methylated by Carcinogens in Vivo and Its Possible Significance in Mutagenesis and Carcinogenesis
The methylating carcinogens can be classified into two broad groups according to their chemical reactivities—those typifying Ingold’s SN2 alkylating agents, such as methyl methanesulfonate and dimethyl sulfate, and those such as N-methyl-N-nitrosourea and N-methyl-N’-nitro-N-nitrosoguanidine, envisaged to methylate through the highly reactive methyldiazonium ion, often described as SN 1 agents. These differences in reaction mechanism are reflected in different ratios of methylation products formed in DNA. It should be noted that dimethylnitrosamine requires metabolic activation to yield the same methylating species as generated by hydrolysis of N-methyl-N-nitrosourea. The principal distinction of the SN 1 agents is their ability to alkylate 0-atom sites in nucleic acids, including the O-6 atom of guanine (reviewed by Lawley, 1972) and phosphodiester groups (Shooter et al., 1974).
KeywordsAlkylating Agent Methane Sulfonate Dimethyl Sulfate Chemical Hydrolysis Methyl Methane Sulfonate
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