Adducts of 6-methylbenzo[a]pyrene and 6-fluorobenzo[a]pyrene formed by electrochemical oxidation in the presence of deoxyribonucleosides.

Studies of the DNA adducts of benzo[a]pyrene and selected derivatives are part of the strategy to elucidate mechanisms of tumor initiation by aromatic hydrocarbons. Reference adducts formed by reaction of deoxyribonucleosides with electrophilic intermediates of 6-fluorobenzo[a]pyrene (6-FBP) and 6-methylbenzo[a]pyrene (6-CH3BP) are investigated here because they are essential for identifying the structures of adducts formed in biological systems. Electrochemical oxidation of 6-FBP in the presence of deoxyribonucleosides led to adducts from the 6-FBP radical cation. With dG, a mixture of 6-FBP bound at C-1 or C-3 to the N-7 of Gua was formed in 10% yield, whereas 6-FBP plus dC gave a mixture of 3-(6-FBP-1-yl)Cyt and 3-(6-FBP-3-yl)Cyt (15%). No adducts of 6-FBP were formed with dA or dT. Electrochemical oxidation of 6-CH3BP in the presence of dG produced 8-(BP-6-CH2-yl)dG (5%) and a mixture of 7-(6-CH3BP-1-yl)Gua and 7-(6-CH3BP-3-yl)Gua (23%). The only adduct formed with dA was 3-(BP-6-CH2-yl)Ade (9%). 6-CH3BP did not afford any adducts with dC or dT. The noncarcinogenic 6-ClBP and 6-BrBP did not produce adducts with dG, dA, dC, or dT. These results are consistent with the chemical properties of the 6-FBP and 6-CH3BP radical cations: that is, 6-FBP reacts at C-1 and C-3, whereas 6-CH3BP reacts competitively at C-1 and C-3, as well as at the 6-CH3 position.