The possible action of carbon-centered radicals in promoting damage to DNA is explored by generation of the 2-phenylethyl radical. The radical is generated during oxidation of phenelzine (2-phenylethyl hydrazine) by ferricyanide, as well as optically from phenylpropionic acid. Covalent binding of the 2-phenylethyl radical to DNA is suggested by studies with the plasmid pBR 322 DNA. Other sensitive techniques used to study DNA damage were the interaction with formaldehyde at 60 degrees C and the fluorescence of DNA-Tb(III) and DNA-DAPI complexes. Theoretical MNDO calculations indicated a preferential attack at position 8 of the guanine residues. This study shows that the 2-phenylethyl radical is able to induce primary effects on nucleic acid structure, leading to alkylated products, especially at purine rings.19431-40