Preferential alkylation by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) of guanines with guanines as neighboring bases in DNA.

The base sequence of DNA has been shown to influence the kinds and amounts of alkylation of purine bases by N-methyl-N-nitrosourea [W. T. Briscoe and L-E. Cotter, Chem. Biol. Interact. 56, 321 (1985)]. In the present study, the alkylation of DNA polymers of defined sequence by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) has been investigated. The assay involved treating poly (dG).poly(dC), poly(dG-dC).poly(dG-dC), poly(dA-dC).poly(dG-dT), poly(dA-dG).poly(dC-dT), and calf thymus DNA with BCNU, followed by hydrolysis to release the modified purine bases and separation and quantitation of these by HPLC. Analysis of the results revealed that there was a 24-fold increase of 7-(beta-hydroxyethyl)guanine (HOEtG) in poly(dG).poly(dC) relative to poly(dA-dG).poly(dC-dT). There was also a 3-fold increase in HOEtG in poly(dG-dC).poly(dG-dC), poly(dA-dC).poly(dG-dT) and calf thymus DNA relative to poly(dA-dG).poly(dC-dT). A 2- to 4-fold increase of 7(beta-aminoethyl)guanine (AmEtG) was observed in poly(dG-dC).poly(dG-dC) relative to the other polymers tested. This study has determined that guanines in certain base sequences in polydeoxyribonucleotides are more susceptible to BCNU alkylation at the N-7 position than guanines in other sequences.