Reactions of the aziridinium ion of mechlorethamine (A(z)(+1)) at the N7, N3 and O6 sites of guanine, N7, N3 and N1 sites of adenine, 02 and N3 sites of cytosine, and O2 and O4 sites of thymine were studied using density functional theory (B3LYP) and the MP2 method in gas phase and aqueous media. The calculations explain the mechanism of alkylation of the DNA bases and show that the reactions of the A(z)(+1) ion would be most likely to occur at the N7 site of guanine and the N3 site of adenine while it would be much less likely to occur at z the carbonyl oxygen sites of the DNA bases. (C) 2007 Elsevier B.V. All rights reserved.