The Mechanism of Nucleoside-alkylation by Alkylnitrosourea -Reaction of 2'-Deoxyguanosine with N -Nitroso-N-methyl-N'-phenylurea in Methanol-

Abstract

The reaction of 2'-deoxyguanosine with N-nitroso-N-methyl-N'-phenylurea 1 in methanol gavo hree alkylated products, N1-(15%), N7-(19%), and O⁶-(24%)methy1-2'-deoxyguanosine, diffe ring rom the result in the reaction with methyl iodide in which only the N⁷-methyl derivative was obtained The random distribution of the products may be due to the formation of a carbonium ion from 1, being mpable of the occurrence of the, S_N1 reaction at the nucleophilic sites in the guanine residue. The rela ive extent of the O⁶-alkylation (O⁶/N¹, O⁶/N⁷) was found to be decreased significantly when the water was added to the reaction medium. This observation suggests that the importance of the O⁶-alkylation will grow further if the DNA-alkylations by alkylnitrosoureas occur in hydrophobic environment Lnder certain cellular conditions. Thus the evaluation of the carcinogenicity of alkylnitro soureas may veil be achieved with properly defined experimental conditions including a solvent or a dosage method