IDENTIFICATION OF N2-SUBSTITUTED 2'-DEOXYGUANOSINE-3'-PHOSPHATE ADDUCTS DETECTED BY P-32 POSTLABELING OF STYRENE-OXIDE-TREATED DNA

Styrene-7,8-oxide, a metabolite of the industrial chemical styrene, was reacted with calf thymus DNA. Six adducts were detected by P-32-postlabeling. The two diastereomers of N2-(2-hydroxy-1-phenylethyl)-2'-deoxyguanosine-3'-phosphate and the corresponding N-1 substituted compounds were isolated from the aqueous reaction mixture of 2'-deoxy-guanosine-3'-phosphate and styrene-7,8-oxide (pH 10.5) and characterized by liquid secondary-ion and four-sector tandem mass spectrometry, ultraviolet, circular dichroism, and fluorescence spectrophotometry, and P-32-postlabeling. Co-chromatography of the DNA-styrene-7,8-oxide reaction products with the synthetic standards showed that adduct no. 6 arose as a result of aralkylation at the N2-exocyclic site of the guanine base. The recovery of the N2-adduct was dependent on the concentration of the solvent used during octadecylsilyl chromatography. These studies revealed that the N2-guanosine derivatives are the major products of the reaction of DNA and styrene-7,8-oxide in vitro detected by P-32-postlabeling.