Abstract
Some unsolved problems in DNA alkylation by N-nitroso compounds are discussed in this overview. Does O6 alkylation of guanine represent the initiating event exclusively or are O4 alkylation of thymidine and phosphate triester formation also involved in the initiating process? Does the formation of rearranged DNA alkylation products by longer chained alkylnitroso compounds have any significance for the carcinogenic effects of these compounds? The concept of hard and soft acids and bases (HSAB principle) as a qualitative model can predict the changes in the DNA alkylation pattern by branched carbenium ions.